Commentary

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Dermatologists have long relied on oral antibiotics to manage moderate to severe acne^1-4; however, it is critical to reassess how these medications are used in clinical practice as concerns about antibiotic resistance grow.⁵ The question is not whether antibiotics are effective for acne treatment—we know they are—but how to optimize their use to balance clinical benefit with responsible prescribing. Resistance in Cutibacterium acnes has been well documented in laboratory settings, but clinical treatment failure due to resistance remains rare and difficult to quantify.^6,7 Still, minimizing unnecessary exposure is good clinical practice. Whether antibiotic resistance ultimately proves to drive clinical failure or remains largely theoretical, stewardship safeguards future treatment options.

In this article, we present a practical, expert-based framework aligned with American Academy of Dermatology (AAD) guidelines to support responsible antibiotic use in acne management. Seven prescribing principles are outlined to help clinicians maintain efficacy while minimizing resistance risk. Mechanisms of resistance in C acnes and broader microbiome impacts also are discussed.

MECHANISMS OF RESISTANCE IN ACNE THERAPY

Antibiotic resistance in acne primarily involves C acnes and arises through selective pressure from prolonged or subtherapeutic antibiotic exposure. Resistance mechanisms include point mutations in ribosomal binding sites, leading to decreased binding affinity for tetracyclines and macrolides as well as efflux pump activation and biofilm formation.^8,9 Over time, resistant strains may proliferate and outcompete susceptible populations, potentially contributing to reduced clinical efficacy. Importantly, the use of broad-spectrum antibiotics may disrupt the skin and gut microbiota, promoting resistance among nontarget organisms.⁵ These concerns underscore the importance of limiting antibiotic use to appropriate indications, combining antibiotics with adjunctive nonantibiotic therapies, and avoiding monotherapy.

PRESCRIBING PRINCIPLES FOR RESPONSIBLE ORAL ANTIBIOTIC USE IN ACNE

The following principles are derived from our clinical experience and are aligned with AAD guidelines on acne treatment.¹⁰ This practical framework supports safe, effective, and streamlined prescribing.

Reserve Oral Antibiotics for Appropriate Cases

Oral antibiotics should be considered for patients with moderate to severe inflammatory acne when rapid anti-inflammatory control is needed. They are not indicated for comedonal or mild papulopustular acne. Before initiating treatment, clinicians should weigh the potential benefits against the risks associated with antibiotic exposure, including resistance and microbiome disruption.

Combine Oral Antibiotics With Topical Retinoids

Oral antibiotics should not be used as monotherapy. Topical retinoids should be initiated concurrently with oral antibiotics to maximize anti-inflammatory benefit, support transition to maintenance therapy, and reduce risk for resistance.

Consider Adding an Adjunctive Topical Antimicrobial Agent

Adjunctive topical antimicrobials can help reduce bacterial load. Benzoyl peroxide remains a first-line option due to its bactericidal activity and lack of resistance induction; however, recent product recalls involving benzene contamination may have raised safety concerns among some clinicians and patients.^11,12 While no definitive harm has been established, alternative topical agents approved by the US Food and Drug Administration (eg, azelaic acid) may be used based on shared decision-making, tolerability, cost, access, and patient preference. Use of topical antibiotics (eg, clindamycin, erythromycin) as monotherapy is discouraged due to their higher resistance potential, which is consistent with AAD guidance.

Limit Treatment Duration to 12 Weeks or Less

Antibiotic use should be time limited, with discontinuation ideally within 8 to 12 weeks as clinical improvement is demonstrated. Repeated or prolonged courses should be avoided to minimize risk for resistance.

Simplify Treatment Regimens to Enhance Adherence

Regimen simplicity improves adherence, especially in adolescents. A two-agent regimen of an oral antibiotic and a topical retinoid typically is sufficient during the induction phase.^13,14

Select Narrower-Spectrum Antibiotics When Feasible

Using a narrower-spectrum antibiotic may help minimize disruption to nontarget microbiota.^15,16 Sarecycline has shown narrower in vitro activity within the tetracycline class,^17,18 though clinical decisions should be informed by access, availability, and cost. Regardless of the agent used (eg, doxycycline, minocycline, or sarecycline), all antibiotics should be used judiciously and for the shortest effective duration.

Use Systemic Nonantibiotic Therapies When Appropriate

If there is inadequate response to oral antibiotic therapy, consider switching to systemic nonantibiotic options. Hormonal therapy may be appropriate for select female patients. Oral isotretinoin should be considered for patients with severe, recalcitrant, or scarring acne. Cycling between antibiotic classes without clear benefit is discouraged.

FINAL THOUGHTS

Oral antibiotics remain a foundational component in the management of moderate to severe acne; however, their use must be intentional, time limited, and guided by best practices to minimize the emergence of antimicrobial resistance. By adhering to the prescribing principles we have outlined here, which are rooted in clinical expertise and consistent with AAD guidelines, dermatologists can preserve antibiotic efficacy, optimize patient outcomes, and reduce long-term microbiologic risks. Stewardship is not about withholding treatment; it is about optimizing care today to protect treatment options for tomorrow.

Pediatric alopecia areata (AA) is a chronic autoimmune disease of the hair follicles characterized by nonscarring hair loss. Its incidence in children in the United States ranges from 13.6 to 33.5 per 100,000 person-years, with a prevalence of 0.04% to 0.11%.¹ Alopecia areata has important effects on quality of life, particularly in children. Hair loss at an early age can decrease participation in school, sports, and extracurricular activities² and is associated with increased rates of comorbid anxiety and depression.³ Families also experience psychosocial stress, often comparable to other chronic pediatric illnesses.⁴ Thus, management requires not only medical therapy but also psychosocial support and school-based accommodations.

Systemic therapies for treatment of AA in adolescents and adults are increasingly available, including US Food and Drug Administration (FDA)–approved Janus kinase (JAK) inhibitors such as baricitinib, deuruxolitinib (for adults), and ritlecitinib (for adolescents and adults); however, no systemic therapies have been approved by the FDA for children younger than 12 years. The therapeutic gap is most acute for those aged 6 to 11 years, for whom the psychosocial burden is high but treatment options are limited.³

This article highlights options and strategies for managing AA in children aged 6 to 11 years, emphasizing supportive and psychosocial care (including camouflage techniques), topical therapies, and off-label systemic approaches.

Supportive and Psychosocial Care

Treatment of AA in children extends beyond the affected child to include parents, caregivers, and even school staff (eg, teachers, principals, nurses).⁴ Disease-specific organizations such as the National Alopecia Areata Foundation ­(naaf.org) and the Children’s Alopecia Project (childrensalopeciaproject.org) provide ­education, support groups, and advocacy resources. These organizations assist families in navigating school accommodations, including Section 504 plans that may allow children with AA to wear hats in school to mitigate stigma. Additional resources include handouts for teachers and school nurses developed by the Society for Pediatric Dermatology.⁵

Psychological support for these patients is critical. Many children benefit from seeing a psychologist, particularly if anxiety, depression, and/or bullying is present.³ In clinics without embedded psychology services, dermatologists should maintain referral lists or encourage families to seek guidance from their pediatrician.

Camouflage techniques can help children cope with visible hair loss. Wigs and hairpieces are available free of charge through charitable organizations for patients younger than 17; however, young children often find adhesives uncomfortable, and they will not wear nonadherent wigs for long periods of time. Alternatives include soft hats, bonnets, scarves, and beanies. For partial hair loss, root concealers, scalp powders, or hair mascara can be useful. Temporary eyebrow tattoos are a good cosmetic approach, whereas microblading generally is not advised in children younger than 12 due to procedural risks including pain.

Topical Therapies

Topical agents remain the mainstay of treatment for AA in children aged 6 to 11 years. Potent class 1 or class 2 topical corticosteroids commonly are used, sometimes in combination with calcineurin inhibitors or topical minoxidil. Off-label compounded topical JAK inhibitors also have been tried in this population and may be helpful for eyebrow hair loss,⁶ though data on their efficacy for scalp AA are mixed.⁷ Intralesional corticosteroid injections, effective in adolescents and adults, generally are poorly tolerated by younger children and may cause considerable distress. Contact immunotherapy with squaric acid dibutyl ester or anthralin can be considered, but these agents are designed to elicit irritation, which may be intolerable for young children.⁸ Shared decision-making with families is essential to balance efficacy, tolerability, and treatment burden.

Systemic Therapies

Systemic therapy generally is reserved for children with extensive or refractory AA. Low-dose oral minoxidil is emerging as an off-label option. One systematic review reported that low-dose oral minoxidil was well tolerated in pediatric patients with minimal adverse effects.⁹ Doses of 0.01 to 0.02 mg/kg/d are reasonable starting points, achieved by cutting tablets or compounding oral solutions.¹⁰

In children with AA and concurrent atopic dermatitis, dupilumab may offer dual benefit. A real-world observational study demonstrated hair regrowth in pediatric patients with AA treated with dupilumab.¹¹ Immunosuppressive options such as low-dose methotrexate or pulse corticosteroids (dexamethasone or prednisolone) also may be considered, although use of these agents requires careful monitoring due to increased risk for infection, clinically significant blood count and liver enzyme changes, and metabolic adverse effects related to long-term use of corticosteroids.

Clinical trials of JAK inhibitors in children aged 6 to 11 years are anticipated to begin in late 2025. Until then, off-label use of ritlecitinib, baricitinib, tofacitinib, or other JAK inhibitors may be considered in select cases with considerable disease burden and quality-of-life impairment following thorough discussion with the patient and their caregivers. Currently available pediatric data show few serious adverse events in children—the most common included upper respiratory infections (nasopharyngitis), acne, and headaches—but long-term risks remain unknown. Dosing challenges also exist for children who cannot swallow pills; currently ritlecitinib is available only as a capsule that cannot be opened while other JAK inhibitors are available in more accessible forms (baricitinib can be crushed and dissolved, and tofacitinib is available in liquid formulation for other pediatric indications). Insurance coverage is a major barrier, as these therapies are not FDA approved for AA in this age group.

Final Thoughts

Alopecia areata in children aged 6 to 11 years presents unique therapeutic challenges. While highly effective systemic therapies exist for older patients, younger children have limited options. For the 6-to-11 age group, management strategies should prioritize psychosocial support, topical therapy, and low-burden systemic alternatives such as low-dose oral minoxidil. Family education, school-based accommodations, and access to camouflage techniques are integral to holistic care. The commencement of pediatric clinical trials for JAK inhibitors offers hope for more robust treatment strategies in the near future. In the meantime, clinicians must engage in shared decision-making, tailoring therapy to the child’s disease severity, emotional well-being, and family priorities.

Pediatric alopecia areata (AA) is a chronic autoimmune disease of the hair follicles characterized by nonscarring hair loss. Its incidence in children in the United States ranges from 13.6 to 33.5 per 100,000 person-years, with a prevalence of 0.04% to 0.11%.¹ Alopecia areata has important effects on quality of life, particularly in children. Hair loss at an early age can decrease participation in school, sports, and extracurricular activities² and is associated with increased rates of comorbid anxiety and depression.³ Families also experience psychosocial stress, often comparable to other chronic pediatric illnesses.⁴ Thus, management requires not only medical therapy but also psychosocial support and school-based accommodations.

Systemic therapies for treatment of AA in adolescents and adults are increasingly available, including US Food and Drug Administration (FDA)–approved Janus kinase (JAK) inhibitors such as baricitinib, deuruxolitinib (for adults), and ritlecitinib (for adolescents and adults); however, no systemic therapies have been approved by the FDA for children younger than 12 years. The therapeutic gap is most acute for those aged 6 to 11 years, for whom the psychosocial burden is high but treatment options are limited.³

This article highlights options and strategies for managing AA in children aged 6 to 11 years, emphasizing supportive and psychosocial care (including camouflage techniques), topical therapies, and off-label systemic approaches.

Supportive and Psychosocial Care

Treatment of AA in children extends beyond the affected child to include parents, caregivers, and even school staff (eg, teachers, principals, nurses).⁴ Disease-specific organizations such as the National Alopecia Areata Foundation ­(naaf.org) and the Children’s Alopecia Project (childrensalopeciaproject.org) provide ­education, support groups, and advocacy resources. These organizations assist families in navigating school accommodations, including Section 504 plans that may allow children with AA to wear hats in school to mitigate stigma. Additional resources include handouts for teachers and school nurses developed by the Society for Pediatric Dermatology.⁵

Psychological support for these patients is critical. Many children benefit from seeing a psychologist, particularly if anxiety, depression, and/or bullying is present.³ In clinics without embedded psychology services, dermatologists should maintain referral lists or encourage families to seek guidance from their pediatrician.

Camouflage techniques can help children cope with visible hair loss. Wigs and hairpieces are available free of charge through charitable organizations for patients younger than 17; however, young children often find adhesives uncomfortable, and they will not wear nonadherent wigs for long periods of time. Alternatives include soft hats, bonnets, scarves, and beanies. For partial hair loss, root concealers, scalp powders, or hair mascara can be useful. Temporary eyebrow tattoos are a good cosmetic approach, whereas microblading generally is not advised in children younger than 12 due to procedural risks including pain.

Topical Therapies

Topical agents remain the mainstay of treatment for AA in children aged 6 to 11 years. Potent class 1 or class 2 topical corticosteroids commonly are used, sometimes in combination with calcineurin inhibitors or topical minoxidil. Off-label compounded topical JAK inhibitors also have been tried in this population and may be helpful for eyebrow hair loss,⁶ though data on their efficacy for scalp AA are mixed.⁷ Intralesional corticosteroid injections, effective in adolescents and adults, generally are poorly tolerated by younger children and may cause considerable distress. Contact immunotherapy with squaric acid dibutyl ester or anthralin can be considered, but these agents are designed to elicit irritation, which may be intolerable for young children.⁸ Shared decision-making with families is essential to balance efficacy, tolerability, and treatment burden.

Systemic Therapies

Systemic therapy generally is reserved for children with extensive or refractory AA. Low-dose oral minoxidil is emerging as an off-label option. One systematic review reported that low-dose oral minoxidil was well tolerated in pediatric patients with minimal adverse effects.⁹ Doses of 0.01 to 0.02 mg/kg/d are reasonable starting points, achieved by cutting tablets or compounding oral solutions.¹⁰

In children with AA and concurrent atopic dermatitis, dupilumab may offer dual benefit. A real-world observational study demonstrated hair regrowth in pediatric patients with AA treated with dupilumab.¹¹ Immunosuppressive options such as low-dose methotrexate or pulse corticosteroids (dexamethasone or prednisolone) also may be considered, although use of these agents requires careful monitoring due to increased risk for infection, clinically significant blood count and liver enzyme changes, and metabolic adverse effects related to long-term use of corticosteroids.

Clinical trials of JAK inhibitors in children aged 6 to 11 years are anticipated to begin in late 2025. Until then, off-label use of ritlecitinib, baricitinib, tofacitinib, or other JAK inhibitors may be considered in select cases with considerable disease burden and quality-of-life impairment following thorough discussion with the patient and their caregivers. Currently available pediatric data show few serious adverse events in children—the most common included upper respiratory infections (nasopharyngitis), acne, and headaches—but long-term risks remain unknown. Dosing challenges also exist for children who cannot swallow pills; currently ritlecitinib is available only as a capsule that cannot be opened while other JAK inhibitors are available in more accessible forms (baricitinib can be crushed and dissolved, and tofacitinib is available in liquid formulation for other pediatric indications). Insurance coverage is a major barrier, as these therapies are not FDA approved for AA in this age group.

Final Thoughts

Alopecia areata in children aged 6 to 11 years presents unique therapeutic challenges. While highly effective systemic therapies exist for older patients, younger children have limited options. For the 6-to-11 age group, management strategies should prioritize psychosocial support, topical therapy, and low-burden systemic alternatives such as low-dose oral minoxidil. Family education, school-based accommodations, and access to camouflage techniques are integral to holistic care. The commencement of pediatric clinical trials for JAK inhibitors offers hope for more robust treatment strategies in the near future. In the meantime, clinicians must engage in shared decision-making, tailoring therapy to the child’s disease severity, emotional well-being, and family priorities.

Pediatric alopecia areata (AA) is a chronic autoimmune disease of the hair follicles characterized by nonscarring hair loss. Its incidence in children in the United States ranges from 13.6 to 33.5 per 100,000 person-years, with a prevalence of 0.04% to 0.11%.¹ Alopecia areata has important effects on quality of life, particularly in children. Hair loss at an early age can decrease participation in school, sports, and extracurricular activities² and is associated with increased rates of comorbid anxiety and depression.³ Families also experience psychosocial stress, often comparable to other chronic pediatric illnesses.⁴ Thus, management requires not only medical therapy but also psychosocial support and school-based accommodations.

Systemic therapies for treatment of AA in adolescents and adults are increasingly available, including US Food and Drug Administration (FDA)–approved Janus kinase (JAK) inhibitors such as baricitinib, deuruxolitinib (for adults), and ritlecitinib (for adolescents and adults); however, no systemic therapies have been approved by the FDA for children younger than 12 years. The therapeutic gap is most acute for those aged 6 to 11 years, for whom the psychosocial burden is high but treatment options are limited.³

This article highlights options and strategies for managing AA in children aged 6 to 11 years, emphasizing supportive and psychosocial care (including camouflage techniques), topical therapies, and off-label systemic approaches.

Supportive and Psychosocial Care

Treatment of AA in children extends beyond the affected child to include parents, caregivers, and even school staff (eg, teachers, principals, nurses).⁴ Disease-specific organizations such as the National Alopecia Areata Foundation ­(naaf.org) and the Children’s Alopecia Project (childrensalopeciaproject.org) provide ­education, support groups, and advocacy resources. These organizations assist families in navigating school accommodations, including Section 504 plans that may allow children with AA to wear hats in school to mitigate stigma. Additional resources include handouts for teachers and school nurses developed by the Society for Pediatric Dermatology.⁵

Psychological support for these patients is critical. Many children benefit from seeing a psychologist, particularly if anxiety, depression, and/or bullying is present.³ In clinics without embedded psychology services, dermatologists should maintain referral lists or encourage families to seek guidance from their pediatrician.

Camouflage techniques can help children cope with visible hair loss. Wigs and hairpieces are available free of charge through charitable organizations for patients younger than 17; however, young children often find adhesives uncomfortable, and they will not wear nonadherent wigs for long periods of time. Alternatives include soft hats, bonnets, scarves, and beanies. For partial hair loss, root concealers, scalp powders, or hair mascara can be useful. Temporary eyebrow tattoos are a good cosmetic approach, whereas microblading generally is not advised in children younger than 12 due to procedural risks including pain.

Topical Therapies

Topical agents remain the mainstay of treatment for AA in children aged 6 to 11 years. Potent class 1 or class 2 topical corticosteroids commonly are used, sometimes in combination with calcineurin inhibitors or topical minoxidil. Off-label compounded topical JAK inhibitors also have been tried in this population and may be helpful for eyebrow hair loss,⁶ though data on their efficacy for scalp AA are mixed.⁷ Intralesional corticosteroid injections, effective in adolescents and adults, generally are poorly tolerated by younger children and may cause considerable distress. Contact immunotherapy with squaric acid dibutyl ester or anthralin can be considered, but these agents are designed to elicit irritation, which may be intolerable for young children.⁸ Shared decision-making with families is essential to balance efficacy, tolerability, and treatment burden.

Systemic Therapies

Systemic therapy generally is reserved for children with extensive or refractory AA. Low-dose oral minoxidil is emerging as an off-label option. One systematic review reported that low-dose oral minoxidil was well tolerated in pediatric patients with minimal adverse effects.⁹ Doses of 0.01 to 0.02 mg/kg/d are reasonable starting points, achieved by cutting tablets or compounding oral solutions.¹⁰

In children with AA and concurrent atopic dermatitis, dupilumab may offer dual benefit. A real-world observational study demonstrated hair regrowth in pediatric patients with AA treated with dupilumab.¹¹ Immunosuppressive options such as low-dose methotrexate or pulse corticosteroids (dexamethasone or prednisolone) also may be considered, although use of these agents requires careful monitoring due to increased risk for infection, clinically significant blood count and liver enzyme changes, and metabolic adverse effects related to long-term use of corticosteroids.

Clinical trials of JAK inhibitors in children aged 6 to 11 years are anticipated to begin in late 2025. Until then, off-label use of ritlecitinib, baricitinib, tofacitinib, or other JAK inhibitors may be considered in select cases with considerable disease burden and quality-of-life impairment following thorough discussion with the patient and their caregivers. Currently available pediatric data show few serious adverse events in children—the most common included upper respiratory infections (nasopharyngitis), acne, and headaches—but long-term risks remain unknown. Dosing challenges also exist for children who cannot swallow pills; currently ritlecitinib is available only as a capsule that cannot be opened while other JAK inhibitors are available in more accessible forms (baricitinib can be crushed and dissolved, and tofacitinib is available in liquid formulation for other pediatric indications). Insurance coverage is a major barrier, as these therapies are not FDA approved for AA in this age group.

Final Thoughts

Alopecia areata in children aged 6 to 11 years presents unique therapeutic challenges. While highly effective systemic therapies exist for older patients, younger children have limited options. For the 6-to-11 age group, management strategies should prioritize psychosocial support, topical therapy, and low-burden systemic alternatives such as low-dose oral minoxidil. Family education, school-based accommodations, and access to camouflage techniques are integral to holistic care. The commencement of pediatric clinical trials for JAK inhibitors offers hope for more robust treatment strategies in the near future. In the meantime, clinicians must engage in shared decision-making, tailoring therapy to the child’s disease severity, emotional well-being, and family priorities.

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Dear Friends,

Since moving to Missouri a little over 2 years ago, I got involved with the Missouri GI Society. They held their inaugural in-person meeting in September, and it was exciting to see and meet gastroenterologists and associates from all over the state. The meeting sparked conversations about challenges in practices and ways to improve patient care. It was incredibly inspiring to see the beginnings and bright future of a society motivated to mobilize change in the community. On a national scale, AGA Advocacy Day 2025 this fall was another example of how to make an impact for the field. I am grateful that local and national GI communities can be a platform for our voices.

In this issue’s “In Focus,” Dr. Colleen R. Kelly discusses the approach for weight management for the gastroenterologist, including how to discuss lifestyle modifications, anti-obesity medications, endoscopic therapies, and bariatric surgeries. In the “Short Clinical Review,” Dr. Ekta Gupta, Dr. Carol Burke, and Dr. Carole Macaron review available non-invasive blood and stool tests for colorectal cancer screening, including guidelines recommendations and evidence supporting each modality.

In the “Early Career” section, Dr. Mayada Ismail shares her personal journey in making the difficult decision of leaving her first job as an early career gastroenterologist, outlining the challenges and lessons learned along the way.

Dr. Alicia Muratore, Dr. Emily V. Wechsler, and Dr. Eric D. Shah provide a practical guide to tech and device development in the “Finance/Legal” section of this issue, outlining everything from intellectual property ownership to building the right team, and selecting the right incubator.

If you are interested in contributing or have ideas for future TNG topics, please contact me (tjudy@wustl.edu) or Danielle Kiefer (dkiefer@gastro.org), Communications/Managing Editor of TNG.

 

Until next time, I leave you with a historical fun fact because we would not be where we are now without appreciating where we were: screening colonoscopy for colorectal cancer was only first introduced in the mid-1990s with Medicare coverage for high-risk individuals starting in 1998, followed by coverage for average-risk patients in 2001.

Yours truly, 

Judy A. Trieu, MD, MPH

Editor-in-Chief

Assistant Professor of Medicine

Interventional Endoscopy, Division of Gastroenterology

Washington University School of Medicine in St. Louis

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

A version of this article first appeared on Medscape.com.

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

A version of this article first appeared on Medscape.com.

Recent studies have cited an alarming increase in early-onset colorectal cancer (CRC) rates, raising concern among gastroenterologists, public health experts, and patients alike. Approximately 10% of CRC cases now occur in those under age 50, and that proportion continues to grow. Between 2000 and 2016, colon cancer rose by 13% and rectal cancer by 16% among those aged 40–49.

According to recently published data from the Surveillance, Epidemiology and End Results Program, between 2019 and 2022, CRC incidence among patients aged 45–49 rose by approximately 12% per year. 
 

A Potential Bacterial Connection

What accounts for this disturbing spike? A research group from the University of California, San Diego, may have uncovered part of the answer.

In their study of 981 CRC genomes, most carried mutations suggestive of prior exposure to colibactin, a toxin produced by certain Escherichia coli (E coli) strains. Patients with extremely early-onset CRC (aged < 40 years) were 3 times more likely to have colibactin-suggestive mutations than patients older than 70. Crucially, colonic exposure to colibactin was linked to an adenomatous polyposis coli driver mutation. 

These findings suggest that colibactin-induced injury in the gut microbiome may accelerate cancer development in some individuals. Environmental factors may contribute to the rise in early-onset CRC as well, such as consuming red meats, carcinogens from grilling, and processed meats and other highly processed foods; low fiber intake; lack of fruits and vegetables; drinking alcohol; lack of exercise; obesity; and colibactin exposure. 

In this video, we will take a closer look at how E coli and colibactin may increase CRC risk.
 

Bacteria’s Cancer-Causing Properties

The idea that bacteria has cancer-causing properties isn’t new. In the 1970s, researchers linked Streptococcus bovis type 1 (now called Streptococcus gallolyticus) to CRC in a subset of patients with bacterial endocarditis stemming from right-sided colon cancer. Similarly, Helicobacter pylori infection has long been associated with increased gastric cancer risk. 

Today, E coli infection is emerging as another possible contributor to CRC, especially via certain pathogenic strains containing the polyketide synthase (pks) genomic island, which encodes the colibactin and is sometimes present in the colon mucosa of patients with CRC.
 

Colibactin and DNA Damage

Colibactin-producing pks+ E coli strains can cause DNA double-strand breaks, one pathway to carcinogenesis. In animal studies, pks+ E coli strains have been linked to both increased risk for CRC and CRC progression.

In an important study published in Nature, Pleguezuelos-Manzano and colleagues repeatedly exposed intestinal organoids to pks+ E coli over 5 months and then performed whole genome sequencing. The result was a concerning potential for short insertions and deletions and single–base substitutions. 

The authors concluded that their “study describes the distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.”

Other E coli virulence factors may also contribute. For example, alpha-hemolysin may downregulate DNA mismatch repair proteins. In other words, E coli is probably just a contributing factor for the development of CRC, not the sole cause. 
 

Biofilms and Inflammation

Previous studies have associated dense bacterial biofilms, particularly antibiotic-resistant strains, with CRC. This raises the possibility that widespread antibiotic overuse could predispose certain individuals to CRC development.

Biofilms normally separate the colon mucosal epithelium from bacteria and are essential for protecting against inflammation. In a 2018 study in Science, Dejea and colleagues concluded that “tumor-prone mice colonized with E coli (expressing colibactin), and enterotoxigenic B fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacteria strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.” 

Additional research revealed that E coli can create a pro-carcinogenic environment by stimulating mucosal inflammation, hindering DNA and mismatch repair mechanisms, and altering immune responses.
 

Dysbiosis and Diet

Colibactin can also drive dysbiosis and imbalance in bacteria in the colon, which fuels inflammation and disrupts mucosal barrier integrity. This creates a vicious cycle in which chronic inflammation can further drive additional mucus deterioration and dysbiosis.

In mouse models where the colon mucosal barrier is damaged with dextrin sulfate sodium (DSS), pks+ E coli gains better access to colon epithelium, causes injury, and can even lead to chronic colitis. Colibactin can also hinder epithelial recovery after DSS treatment. 

Diet plays a central role in this process. Low fiber consumption can disrupt the barrier between the colon mucus layer and the colon’s exterior layer where bacteria live. A traditional Western diet may bolster bacteria that degrade the mucus layer when the bacteria consume the glycosylated portion as an energy source.

Fortunately, diet is modifiable. High–fiber diets (ideally 25-30 g/d) boost short–chain fatty acids in the colon. This is important because short-chain fatty acids can decrease intercellular pH and impede Enterobacteriaceae replication, yet another reason why we should encourage patients to eat a diet high in vegetables, fruits, and [green] salads. 
 

Two Types of Bacterial Drivers 

There appear to be two broad types of bacteria associated with CRC development. It’s been hypothesized that there are “driver” bacteria that might initiate the development of CRC, possibly by creating oxidative stress and causing DNA breaks. Several potential pathogenic bacteria have been identified, including E coli, Enterococcus faecalis, and Bacteroides fragilis. Unfortunately, there are also bacteria such as Fusobacterium species and Streptococcus gallolyticus with the potential to alter intestinal permeability, resulting in downstream effects that can allow colon cancers to expand. Fusobacterium species and Streptococcus gallolyticus have the potential to cause DNA double–strand breaks in the intestine, which can produce chromosomal precariousness. 

These secondary bacteria can also lead to DNA epigenetic changes and gene mutations. However, it should be emphasized that “the direct causation of imprinted DNA changes resulting from a direct interaction between bacteria and host cells is not so far established.”

E coli produces compounds called cyclomodulins, which can cause DNA breaks and potentially trigger cell cycle arrest and even cell death through activation of the DNA damage checkpoint pathway. The DNA damage checkpoint pathway is a cellular signaling network that helps detect DNA lesions and allows for genetic stability by stopping growth to allow for repair and simulating cell survival or apoptosis. A key cyclomodulin that E coli makes is colibactin, produced by the pks locus. Other cyclomodulins include cytolethal distending toxin, cytotoxic necrotizing factor, and cycle-inhibiting factor. 

Previous research has shown that E coli is the only culturable bacteria found near CRC. A groundbreaking 1998 study employing PCR technology found E coli in 60% of colon polyp adenomas and an alarming 77% of CRC biopsies. 

E coli’s capability to downregulate essential DNA mismatch repair proteins has been implicated in colorectal carcinogenesis. Interestingly, when the genetic region responsible for producing colibactin is deleted in animals, the bacteria aren’t able to promote cancer.

Mechanistically, colibactin causes double-stranded DNA breaks, eukaryotic cell cycle arrest, and chromosome abnormalities. It also alkylates DNA. This occurs when the cyclopropane ring of colibactin interacts with the N3 position of adenine in DNA, forming a covalent bond and creating a DNA adduct. DNA adducts occur when a chemical moiety from an environmental or dietary source binds to DNA base. Colibactin can cause DNA interstrand cross-links to form via alkalization of adenine residues on opposing DNA strands, a crucial step in DNA damage. DNA adducts can occur through carcinogens in N-nitroso compounds, such as in processed meats and in polycyclic aromatic hydrocarbons found in cigarette smoke. Colibactin-induced damage may also stimulate the senescence–associated secretory phenotype pathway, increasing proinflammatory cytokines.
 

E coli and Inflammatory Bowel Disease 

E coli, the primary colibactin producer in the human intestinal microbiome, is found at higher bacterial percentages in the microbiomes of patients with inflammatory bowel disease (IBD). In a study by Dubinsky and colleagues, “the medium relative levels of colibactin–encoding E. coli were about threefold higher in IBD.”

Researchers have also postulated that antibiotics and microbiome dysbiosis may create conditions that allow colibactin–producing bacteria to overpopulate.
 

Future Directions

Not every patient with CRC carries a colorectal mutational signature, but these findings underscore the need for continued vigilance and prevention. 

From a public health standpoint, our advice remains consistent: Promote high-fiber diets with more vegetables and less red meat; avoid highly processed foods; avoid alcohol; encourage exercise; and address overweight and obesity. Our goal is to create the best possible colon environment to prevent DNA damage from bacterial and environmental carcinogens.

In the future, we need more research to clarify exactly how E coli and colibactin increase early–onset CRC risk and whether antibiotics and dysbiosis facilitate their ability to damage the DNA of colon mucosa. It’s still unclear why younger patients are at greater risk. In time, we may be able to screen for colibactin–producing bacteria such as E coli and manipulate the fecal microbiome to prevent damage. 

A recent mouse study in Nature by Jans and colleagues suggests it might be possible to block bacterial adhesion and hopefully mitigate damage caused by colibactin. With continued work, colibactin–targeted strategies could become a part of CRC prevention.

Benjamin H. Levy III, MD, is a gastroenterologist at the University of Chicago. In 2017, Levy, a previous Fulbright Fellow in France, also started a gastroenterology clinic for refugees resettling in Chicago. His clinical projects focus on the development of colorectal cancer screening campaigns. Levy, who gave a TEDx Talk about building health education campaigns using music and concerts, organizes "Tune It Up: A Concert To Raise Colorectal Cancer Awareness" with the American College of Gastroenterology (ACG). He frequently publishes on a variety of gastroenterology topics and serves on ACG’s Public Relations Committee and FDA-Related Matters Committee.

A version of this article first appeared on Medscape.com.

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

A version of this article first appeared on Medscape.com.

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

A version of this article first appeared on Medscape.com.

The War on Cancer, declared by President Richard Nixon some 50 years ago, has been canceled during the second Trump administration in 2025 — so saith The New York Times Sunday magazine cover story on September 14, 2025. This war seems now to be best described as "The War on Cancer Research."

To our horror and disbelief, we've witnessed the slow but persistent drift of much of the United States citizenry away from science and the sudden and severe movement of the US government to crush much medical research. But it is not as if we were not warned.

In August 2024, on these pages and without political bias, I urged Medscape readers to pay attention to Project 2025. A great deal of what we as a population are now experiencing was laid out as a carefully constructed plan.

What is surprising is the cruel ruthlessness of the "move fast and break things" approach, taken with little apparent concern about the resultant human tragedies (workforce and patients) and no clear care about the resulting fallout. As we've now learned, destroying something as grand as our cancer research enterprise can be accomplished very quickly. Rebuilding it is certain to be slow and difficult and perhaps can never be accomplished.

In this new anti-science, anti-research, and anti-researcher reality, what can we now do?

First and foremost, we must recognize that the war on cancer is not over. Cancer is not canceled, even if much of the US government's research effort/funding has been. Those of us in medicine and public health often speak in quantification of causes of death of our populations. As such, I'll remind Medscape readers that cancer afflicts some 20 million humans worldwide each year, killing nearly 10 million. Although two-thirds of Americans diagnosed with a potentially lethal malignancy are cured, cancer still kills roughly 600,000 Americans each year. Cancer has been the second most frequent cause of death of Americans for 75 years.

Being inevitable and immutable, death itself is not the enemy. We all die. Disease, disability, pain, and human suffering are the real enemies of us all. Cancer maims, pains, diabetes, and torments some 20 million humans worldwide each year. That is a huge humanitarian problem that should be recognized by individuals of all creeds and backgrounds.

With this depletion of our domestic government basic and applied cancer research program, what can we do?

1. Think globally and look to the international scientific research enterprises — relying on them, much as they have relied on us.
2. Defend the universal importance of reliable and available literature on medical science.
3. Continue to translate and apply the vast amount of available published research in clinical practice and publish the results.
4. Urge private industries to expand their research budgets into areas of study that may not produce quickly tangible positive bottom-line results.
5. Remind the Secretary of the Department of Health and Human Services (for whom chronic diseases seem paramount) that cancer is the second leading American chronic disease by morbidity.
6. Redouble efforts of cancer prevention, especially urging the FDA to ban combustible tobacco and strive more diligently to decrease obesity.
7. Appeal to our vast philanthropic universe to increase its funding of nonprofit organizations active in the cancer investigation, diagnosis, and management space.

One such 501c3 organization is California-based Cancer Commons. (Disclosure: I named it in 2010 and serve as its editor in chief).

A commons is a space shared by a community to use for the common interest. As we originally envisioned it, a cancer commons is an open access internet location where individuals and organizations (eg, corporations, universities, government agencies, philanthropies) will voluntarily share their data to work together to defeat the common enemy of humans: cancer.

On September 8, 2025, Cancer Commons was the 15th annual Lundberg Institute Lecturer at the Commonwealth Club of California in San Francisco. At the lecture, Cancer Commons founder (and long-term survivor of metastatic malignant melanoma), Jay Martin "Martin" Tenenbaum, PhD, spoke of the need for a cancer commons and the founder's vision. Emma Shtivelman, PhD, the long-time compassionate chief scientist, described some of the thousands of patients with advanced cancer that she has helped — all free of charge. And newly named CEO Clifford Reid, MBA, PhD, used his entrepreneurial prowess to envision an ambitious future.

Cancer Commons has always focused on patients with cancer who are beyond standards of curative care. As Cancer Commons evolves, it anticipates focusing on patients with cancer who are beyond National Comprehensive Cancer Network Guidelines. The organization intends to greatly expand its 1000 patients per year with "high touch" engagement with PhD clinical scientists to many thousands by including artificial intelligence. It plans to extend its N-of-One approach to create new knowledge — especially regarding the hundreds of drugs that are FDA-approved for use in treating cancer but have not been further assessed for the utility in actually treating patients with cancer.

The war on cancer is not over. It remains a persistent foe that causes immense disability, pain, and human suffering. With government support depleted, the burden now shifts to the private sector and philanthropic organizations, such as Cancer Commons, to serve as the new vital infrastructure in the fight for a cure. Now, we must redouble our efforts to ensure that these research endeavors are supported if the US government will not do its part.

A version of this article first appeared on Medscape.com.

The practice of medicine is evolving rapidly, with clinicians facing enhanced pressure to maximize productivity while managing increasingly complex patients and related clinical documentation. Indeed, clinicians are spending less time seeing patients, and more time in front of a computer screen.

Despite the many rewards of clinical medicine, rates of clinical practice attrition have increased among physicians in all specialties since 2013 with enhanced administrative burdens identified as a prominent driver. Among its many applications, artificial intelligence (AI) has immense potential to reduce the administrative and cognitive burdens that contribute to clinician burnout and attrition through tools such as AI scribes – these technologies have been rapidly adopted across healthcare systems and are already in use by ~30% of physician practices. The hope is that AI scribes will significantly reduce documentation time, leading to improvements in clinician wellbeing and expanding capacity for patient care. Indeed, some studies have shown up to a 20-30% improvement in documentation efficiency. 

So, is AI a cure for physician burnout? The answer depends on what is done with these efficiency gains. If healthcare organizations respond to this enhanced efficiency by increasing patient volume expectations rather than allowing clinicians to recapture some of this time for meaningful work and professional wellbeing, it could create a so-called “workload paradox” where modest time savings are offset by greater productivity demands and the cognitive burden of reviewing AI-generated errors. While AI offers substantial promise as a tool to reduce administrative burdens, its success will depend on thoughtful and responsible implementation that prioritizes clinician well-being and patient safety in addition to productivity.

In our final issue of 2025, we highlight a recent RCT from Annals of Internal Medicine finding that fecal microbiota transplantation is at least as effective as vancomycin in treating primary C. difficile infection. In this month’s Member Spotlight, we feature Andrew Ofosu, MD, MPH (University of Cincinnati Health), who stresses the importance of transparency and compassion in communicating effectively with patients, particularly around complex diagnoses. We hope you enjoy this and all the exciting content in our December issue.

Megan A. Adams, MD, JD, MSc 

Editor in Chief

The practice of medicine is evolving rapidly, with clinicians facing enhanced pressure to maximize productivity while managing increasingly complex patients and related clinical documentation. Indeed, clinicians are spending less time seeing patients, and more time in front of a computer screen.

Despite the many rewards of clinical medicine, rates of clinical practice attrition have increased among physicians in all specialties since 2013 with enhanced administrative burdens identified as a prominent driver. Among its many applications, artificial intelligence (AI) has immense potential to reduce the administrative and cognitive burdens that contribute to clinician burnout and attrition through tools such as AI scribes – these technologies have been rapidly adopted across healthcare systems and are already in use by ~30% of physician practices. The hope is that AI scribes will significantly reduce documentation time, leading to improvements in clinician wellbeing and expanding capacity for patient care. Indeed, some studies have shown up to a 20-30% improvement in documentation efficiency. 

So, is AI a cure for physician burnout? The answer depends on what is done with these efficiency gains. If healthcare organizations respond to this enhanced efficiency by increasing patient volume expectations rather than allowing clinicians to recapture some of this time for meaningful work and professional wellbeing, it could create a so-called “workload paradox” where modest time savings are offset by greater productivity demands and the cognitive burden of reviewing AI-generated errors. While AI offers substantial promise as a tool to reduce administrative burdens, its success will depend on thoughtful and responsible implementation that prioritizes clinician well-being and patient safety in addition to productivity.

In our final issue of 2025, we highlight a recent RCT from Annals of Internal Medicine finding that fecal microbiota transplantation is at least as effective as vancomycin in treating primary C. difficile infection. In this month’s Member Spotlight, we feature Andrew Ofosu, MD, MPH (University of Cincinnati Health), who stresses the importance of transparency and compassion in communicating effectively with patients, particularly around complex diagnoses. We hope you enjoy this and all the exciting content in our December issue.

Megan A. Adams, MD, JD, MSc 

Editor in Chief

The practice of medicine is evolving rapidly, with clinicians facing enhanced pressure to maximize productivity while managing increasingly complex patients and related clinical documentation. Indeed, clinicians are spending less time seeing patients, and more time in front of a computer screen.

Despite the many rewards of clinical medicine, rates of clinical practice attrition have increased among physicians in all specialties since 2013 with enhanced administrative burdens identified as a prominent driver. Among its many applications, artificial intelligence (AI) has immense potential to reduce the administrative and cognitive burdens that contribute to clinician burnout and attrition through tools such as AI scribes – these technologies have been rapidly adopted across healthcare systems and are already in use by ~30% of physician practices. The hope is that AI scribes will significantly reduce documentation time, leading to improvements in clinician wellbeing and expanding capacity for patient care. Indeed, some studies have shown up to a 20-30% improvement in documentation efficiency. 

So, is AI a cure for physician burnout? The answer depends on what is done with these efficiency gains. If healthcare organizations respond to this enhanced efficiency by increasing patient volume expectations rather than allowing clinicians to recapture some of this time for meaningful work and professional wellbeing, it could create a so-called “workload paradox” where modest time savings are offset by greater productivity demands and the cognitive burden of reviewing AI-generated errors. While AI offers substantial promise as a tool to reduce administrative burdens, its success will depend on thoughtful and responsible implementation that prioritizes clinician well-being and patient safety in addition to productivity.

In our final issue of 2025, we highlight a recent RCT from Annals of Internal Medicine finding that fecal microbiota transplantation is at least as effective as vancomycin in treating primary C. difficile infection. In this month’s Member Spotlight, we feature Andrew Ofosu, MD, MPH (University of Cincinnati Health), who stresses the importance of transparency and compassion in communicating effectively with patients, particularly around complex diagnoses. We hope you enjoy this and all the exciting content in our December issue.

Megan A. Adams, MD, JD, MSc 

Editor in Chief

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.

Are you seeing any increase or trends in cutaneous adverse effects related to the use of GLP-1 agonists in your practice?

DR. SHIELDS: The use of GLP-1 agonists is increasing substantially across numerous populations. Patients are using these medications not only for weight management and diabetes control but also for blood pressure modulation and cardiovascular risk reduction. The market size is expected to grow at a rate of about 6% until 2027. While severe cutaneous adverse effects still are considered relatively rare with GLP-1 agonist use, mild adverse effects are quite common. Dermatologists should be familiar with these effects and how to manage them. Rare but serious cutaneous reactions include morbilliform drug eruptions, dermal hypersensitivity reactions, panniculitis, and bullous pemphigoid. It is thought that some GLP-1 agonists may cause more skin reactions than others; for example, exenatide extended-release has been associated with cutaneous adverse events more frequently than other GLP-1 agonists in a recent comprehensive literature review.

Do you see a role for dermatologists in monitoring or managing the downstream dermatologic effects of GLP-1 agonists over the next few years?

DR. SHIELDS: Absolutely. When patients develop a drug eruption, bullous pemphigoid, or eosinophilic panniculitis, dermatologists are going to be the ones to diagnose and manage therapy. Awareness of these adverse effects is crucial to timely and thoughtful discussions surrounding medication discontinuation vs a “treat through” approach.

Do you recommend coordinating with endocrinologists or obesity medicine specialists when managing shared patients on GLP-1s (particularly if skin concerns arise)?

DR. SHIELDS: Yes. This is crucial to patient success. Co-management can provide clarity around the indication for therapy and allow for a thoughtful risk-benefit discussion with the patient, primary care physician, endocrinologist, cardiologist, etc. In my practice, I have found that many patients do not want to stop therapy even when they develop cutaneous adverse effects. There are options to transition therapy or treat through in some cases, but having a comprehensive monitoring and therapy plan is critical.

Have you encountered cases in which rapid weight loss from GLP-1s worsened conditions such as loose skin, cellulite, or facial lipoatrophy, leading to new aesthetic concerns? How would you recommend counseling and/or treating affected patients?

DR. SHIELDS: Accelerated facial aging is a noticeable adverse effect in patients who undergo treatment with GLP-1 agonists, especially when used off-label for weight loss. Localized loss of facial fat can result in altered facial proportions and excess skin. There are multiple additional mechanisms that may underlie accelerated facial aging in patients on GLP-1s, and really we are just beginning to scratch the surface of why and how this happens. Understanding these mechanisms will open the door to downstream preventive and therapeutic options. If patients experience new aesthetic concerns, I currently work with them to adjust their medication to slow weight loss, recommend improved nutrition and hydration, encourage exercise and weight training to maintain muscle mass, and engage my cosmetic dermatology colleagues to discuss procedures such as dermal fillers.

All patients starting GLP-1 agonists should be thoroughly counseled on risks and adverse effects of their medication. These are well reported and should be considered carefully. Starting with lower medication dosing in conjunction with slow escalation and careful monitoring can be helpful in combatting these adverse effects.