Lymphoma & Plasma Cell Disorders

The telomerase inhibitor imetelstat showed promise against advanced myelofibrosis and essential thrombocythemia in two industry-funded preliminary studies, according to separate reports published online Sept. 3 in the New England Journal of Medicine.

In previous in vitro and animal studies, imetelstat inhibited the proliferation of various types of malignant cells but was not active in normal somatic tissue. Researchers assessed the agent for advanced myelofibrosis in part because, at present, only one available treatment – allogeneic stem-cell transplantation (ASCT) – sometimes induces long-term remission. ASCT carries a relatively high rate of treatment-related death and complications, and is contraindicated in many older patients.

In the first report, researchers conducted a small, single-center cohort study to collect preliminary data on the agent’s efficacy and safety in 33 patients with primary myelofibrosis (18 participants), myelofibrosis that was related to polycythemia (10 participants), or myelofibrosis associated with essential thrombocytopenia (10 participants). Imetelstat was administered in 2-hour intravenous infusions given in 3-week cycles, said Dr. Ayalew Tefferi of the division of hematology, Mayo Clinic, Rochester Minn.

©Ed Uthman/flickr.com

The median duration of treatment was 8.6 months (range, 1.4-21.7 months). Seven patients (21%) had either a complete or partial response; the 4 patients with a complete response had documented complete reversal of bone marrow fibrosis. The time to onset of response was 3.5 months (range, 1.4-7.2 months), and the median duration of response was 18 months (range, 13-20 months).

These remissions “confirm selective anticlonal activity, which has not previously been documented in drug treatment of myelofibrosis,” noted Dr. Tefferi and his associates (N Engl J Med 2015 Sep 3. doi:10.1056/NEJMoa1310523). Three of the seven patients who responded to imetelstat “had been heavily dependent on red-cell transfusions at study entry and became transfusion-independent and sustained a hemoglobin level of more than 10 g/dL for a minimum of 3 months during therapy,” they noted.

In addition, 8 of 10 patients who had marked leukocytosis at baseline had either a complete resolution (3 patients) or a reduction of at least 50% in white-cell counts (5 patients). All 11 participants who had thrombocytosis at baseline had either complete resolution (10 patients) or a reduction in platelet count of at least 50% (1 patient). Of the 27 participants who had leukoerythroblastosis at baseline, 22 showed either complete resolution (13 patients) or a reduction of at least 50% in the percentage of immature myeloid cells and nucleated red cells (9 patients). Also, 17 of the 21 participants who had at least 1% circulating blasts at baseline had either a complete disappearance of circulating blasts (14 patients) or a reduction of at least 50% (3 patients).

The most clinically significant adverse effect of imetelstat, myelosuppression, occurred in 22 patients (67%) and often necessitated dose reductions. Low-grade elevations in liver enzymes also were a concern. One patient died from an intracranial hemorrhage that the treating physician attributed to drug-induced grade 4 thrombocytopenia. Other adverse events that may or may not have been treatment related included fever, epistaxis, bruising, hematoma, lung infection, skin infection, and upper-GI hemorrhage.

These findings not only identify imetelstat as a possible treatment for myelofibrosis, they also suggest that other telomerase-targeting strategies may be beneficial in this disease, Dr. Tefferi and his associates added.

In the second report, researchers performing a phase-II study at seven medical centers in the United States, Germany, and Switzerland found that imetelstat produced rapid and durable hematologic and molecular responses in all 18 patients in their study of essential thrombocythemia refractory to other treatments. This result is particularly encouraging because current standard therapies “induce nonspecific reductions in platelet counts but do not typically eliminate or alter the biologic characteristics of the disease,” said Dr. Gabriela M. Baerlocher of the department of hematology and the Stem Cell Molecular Diagnostics Laboratory, University of Bern, Switzerland.

These study participants had either failed to respond to hydroxyurea, anagrelide, and interferon therapy or were forced to discontinue these agents because of adverse effects. After weekly treatment with imetelstat at one of two doses, 100% of the patients achieved a hematologic response, attaining platelet counts of 250,000-300,000 per cc. Sixteen participants (89%) achieved a complete hematologic response. The median time to complete response was 6.1 weeks, Dr. Baerlocher and her associates said (N Engl J Med. 2015 Sep 3. doi:10.1056/NEJMoa1503479).

After a median follow-up of 17 months on a maintenance dose of imetelstat, 10 patients were still receiving treatment. The median duration of response had not been reached as of press time (range, 5-30 months).

The most important adverse events were neutropenia (15 patients) and abnormal results on liver-function tests (14 patients). The treating physicians attributed 18 adverse events of grade 3 or higher to the study drug, including headache, anemia, and one syncopal episode. Other adverse events included fatigue, nausea, diarrhea, infections, and rash.

The telomerase inhibitor imetelstat showed promise against advanced myelofibrosis and essential thrombocythemia in two industry-funded preliminary studies, according to separate reports published online Sept. 3 in the New England Journal of Medicine.

In previous in vitro and animal studies, imetelstat inhibited the proliferation of various types of malignant cells but was not active in normal somatic tissue. Researchers assessed the agent for advanced myelofibrosis in part because, at present, only one available treatment – allogeneic stem-cell transplantation (ASCT) – sometimes induces long-term remission. ASCT carries a relatively high rate of treatment-related death and complications, and is contraindicated in many older patients.

In the first report, researchers conducted a small, single-center cohort study to collect preliminary data on the agent’s efficacy and safety in 33 patients with primary myelofibrosis (18 participants), myelofibrosis that was related to polycythemia (10 participants), or myelofibrosis associated with essential thrombocytopenia (10 participants). Imetelstat was administered in 2-hour intravenous infusions given in 3-week cycles, said Dr. Ayalew Tefferi of the division of hematology, Mayo Clinic, Rochester Minn.

©Ed Uthman/flickr.com

The median duration of treatment was 8.6 months (range, 1.4-21.7 months). Seven patients (21%) had either a complete or partial response; the 4 patients with a complete response had documented complete reversal of bone marrow fibrosis. The time to onset of response was 3.5 months (range, 1.4-7.2 months), and the median duration of response was 18 months (range, 13-20 months).

These remissions “confirm selective anticlonal activity, which has not previously been documented in drug treatment of myelofibrosis,” noted Dr. Tefferi and his associates (N Engl J Med 2015 Sep 3. doi:10.1056/NEJMoa1310523). Three of the seven patients who responded to imetelstat “had been heavily dependent on red-cell transfusions at study entry and became transfusion-independent and sustained a hemoglobin level of more than 10 g/dL for a minimum of 3 months during therapy,” they noted.

In addition, 8 of 10 patients who had marked leukocytosis at baseline had either a complete resolution (3 patients) or a reduction of at least 50% in white-cell counts (5 patients). All 11 participants who had thrombocytosis at baseline had either complete resolution (10 patients) or a reduction in platelet count of at least 50% (1 patient). Of the 27 participants who had leukoerythroblastosis at baseline, 22 showed either complete resolution (13 patients) or a reduction of at least 50% in the percentage of immature myeloid cells and nucleated red cells (9 patients). Also, 17 of the 21 participants who had at least 1% circulating blasts at baseline had either a complete disappearance of circulating blasts (14 patients) or a reduction of at least 50% (3 patients).

The most clinically significant adverse effect of imetelstat, myelosuppression, occurred in 22 patients (67%) and often necessitated dose reductions. Low-grade elevations in liver enzymes also were a concern. One patient died from an intracranial hemorrhage that the treating physician attributed to drug-induced grade 4 thrombocytopenia. Other adverse events that may or may not have been treatment related included fever, epistaxis, bruising, hematoma, lung infection, skin infection, and upper-GI hemorrhage.

These findings not only identify imetelstat as a possible treatment for myelofibrosis, they also suggest that other telomerase-targeting strategies may be beneficial in this disease, Dr. Tefferi and his associates added.

In the second report, researchers performing a phase-II study at seven medical centers in the United States, Germany, and Switzerland found that imetelstat produced rapid and durable hematologic and molecular responses in all 18 patients in their study of essential thrombocythemia refractory to other treatments. This result is particularly encouraging because current standard therapies “induce nonspecific reductions in platelet counts but do not typically eliminate or alter the biologic characteristics of the disease,” said Dr. Gabriela M. Baerlocher of the department of hematology and the Stem Cell Molecular Diagnostics Laboratory, University of Bern, Switzerland.

These study participants had either failed to respond to hydroxyurea, anagrelide, and interferon therapy or were forced to discontinue these agents because of adverse effects. After weekly treatment with imetelstat at one of two doses, 100% of the patients achieved a hematologic response, attaining platelet counts of 250,000-300,000 per cc. Sixteen participants (89%) achieved a complete hematologic response. The median time to complete response was 6.1 weeks, Dr. Baerlocher and her associates said (N Engl J Med. 2015 Sep 3. doi:10.1056/NEJMoa1503479).

After a median follow-up of 17 months on a maintenance dose of imetelstat, 10 patients were still receiving treatment. The median duration of response had not been reached as of press time (range, 5-30 months).

The most important adverse events were neutropenia (15 patients) and abnormal results on liver-function tests (14 patients). The treating physicians attributed 18 adverse events of grade 3 or higher to the study drug, including headache, anemia, and one syncopal episode. Other adverse events included fatigue, nausea, diarrhea, infections, and rash.

The telomerase inhibitor imetelstat showed promise against advanced myelofibrosis and essential thrombocythemia in two industry-funded preliminary studies, according to separate reports published online Sept. 3 in the New England Journal of Medicine.

In previous in vitro and animal studies, imetelstat inhibited the proliferation of various types of malignant cells but was not active in normal somatic tissue. Researchers assessed the agent for advanced myelofibrosis in part because, at present, only one available treatment – allogeneic stem-cell transplantation (ASCT) – sometimes induces long-term remission. ASCT carries a relatively high rate of treatment-related death and complications, and is contraindicated in many older patients.

In the first report, researchers conducted a small, single-center cohort study to collect preliminary data on the agent’s efficacy and safety in 33 patients with primary myelofibrosis (18 participants), myelofibrosis that was related to polycythemia (10 participants), or myelofibrosis associated with essential thrombocytopenia (10 participants). Imetelstat was administered in 2-hour intravenous infusions given in 3-week cycles, said Dr. Ayalew Tefferi of the division of hematology, Mayo Clinic, Rochester Minn.

©Ed Uthman/flickr.com

The median duration of treatment was 8.6 months (range, 1.4-21.7 months). Seven patients (21%) had either a complete or partial response; the 4 patients with a complete response had documented complete reversal of bone marrow fibrosis. The time to onset of response was 3.5 months (range, 1.4-7.2 months), and the median duration of response was 18 months (range, 13-20 months).

These remissions “confirm selective anticlonal activity, which has not previously been documented in drug treatment of myelofibrosis,” noted Dr. Tefferi and his associates (N Engl J Med 2015 Sep 3. doi:10.1056/NEJMoa1310523). Three of the seven patients who responded to imetelstat “had been heavily dependent on red-cell transfusions at study entry and became transfusion-independent and sustained a hemoglobin level of more than 10 g/dL for a minimum of 3 months during therapy,” they noted.

In addition, 8 of 10 patients who had marked leukocytosis at baseline had either a complete resolution (3 patients) or a reduction of at least 50% in white-cell counts (5 patients). All 11 participants who had thrombocytosis at baseline had either complete resolution (10 patients) or a reduction in platelet count of at least 50% (1 patient). Of the 27 participants who had leukoerythroblastosis at baseline, 22 showed either complete resolution (13 patients) or a reduction of at least 50% in the percentage of immature myeloid cells and nucleated red cells (9 patients). Also, 17 of the 21 participants who had at least 1% circulating blasts at baseline had either a complete disappearance of circulating blasts (14 patients) or a reduction of at least 50% (3 patients).

The most clinically significant adverse effect of imetelstat, myelosuppression, occurred in 22 patients (67%) and often necessitated dose reductions. Low-grade elevations in liver enzymes also were a concern. One patient died from an intracranial hemorrhage that the treating physician attributed to drug-induced grade 4 thrombocytopenia. Other adverse events that may or may not have been treatment related included fever, epistaxis, bruising, hematoma, lung infection, skin infection, and upper-GI hemorrhage.

These findings not only identify imetelstat as a possible treatment for myelofibrosis, they also suggest that other telomerase-targeting strategies may be beneficial in this disease, Dr. Tefferi and his associates added.

In the second report, researchers performing a phase-II study at seven medical centers in the United States, Germany, and Switzerland found that imetelstat produced rapid and durable hematologic and molecular responses in all 18 patients in their study of essential thrombocythemia refractory to other treatments. This result is particularly encouraging because current standard therapies “induce nonspecific reductions in platelet counts but do not typically eliminate or alter the biologic characteristics of the disease,” said Dr. Gabriela M. Baerlocher of the department of hematology and the Stem Cell Molecular Diagnostics Laboratory, University of Bern, Switzerland.

These study participants had either failed to respond to hydroxyurea, anagrelide, and interferon therapy or were forced to discontinue these agents because of adverse effects. After weekly treatment with imetelstat at one of two doses, 100% of the patients achieved a hematologic response, attaining platelet counts of 250,000-300,000 per cc. Sixteen participants (89%) achieved a complete hematologic response. The median time to complete response was 6.1 weeks, Dr. Baerlocher and her associates said (N Engl J Med. 2015 Sep 3. doi:10.1056/NEJMoa1503479).

After a median follow-up of 17 months on a maintenance dose of imetelstat, 10 patients were still receiving treatment. The median duration of response had not been reached as of press time (range, 5-30 months).

The most important adverse events were neutropenia (15 patients) and abnormal results on liver-function tests (14 patients). The treating physicians attributed 18 adverse events of grade 3 or higher to the study drug, including headache, anemia, and one syncopal episode. Other adverse events included fatigue, nausea, diarrhea, infections, and rash.

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Exome and transcriptome sequencing results can inform the management of young patients with relapsed, refractory, and rare malignancies, a new study suggests.

In a consecutive case series, sequencing data revealed potentially actionable findings for 46% of patients.

As a result, 15% of patients changed treatment, and 10% underwent genetic counseling.

Investigators described this research in JAMA.

“We found that, for some children with rare, difficult-to-treat, and aggressive cancers, this technology can dramatically change the course of their treatment,” said study author Rajen Mody, MBBS, of the University of Michigan in Ann Arbor.

Dr Mody and his colleagues evaluated 102 patients with relapsed, refractory, or rare cancers. Their median age was 11.5 (range, 0-22).

The patients underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing. Ninety-one patients (89%) had adequate tumor tissue to complete sequencing, including 28 patients (31%) with hematologic malignancies and 63 (69%) with solid tumors.

All sequencing results were discussed at a precision medicine tumor board, which included pediatric and adult oncologists, pathologists, genetics specialists, and other professionals. This group discussed the results and assessed the feasibility of pursuing treatment options based on the findings.

Actionable findings

Forty-two patients (46%) had potentially actionable findings, 15 (54%) with hematologic malignancies and 27 (43%) with solid tumors.

Actionable findings included a change in diagnosis (n=2), the presence of a genetic anomaly that could be targeted by an approved or experimental drug (n=31), and the need for genetic counseling for inherited cancer risk that could affect the patient or the whole family (n=9).

“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could potentially be higher over time,” said study author Arul Chinnaiyan, MD, PhD, also of the University of Michigan.

“These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis. If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient.”

Actions were taken in 23 of the 42 patients. Fourteen patients (15%) had their treatment changed, and 9 of these patients (10%) had durable partial or complete remissions (CRs) as a result.

Nine patients (10%) underwent genetic counseling because of sequencing results. The researchers noted that 4 of these patients had no notable family history to suggest an inherited risk, and they would not otherwise have been referred for genetic counseling.

Hematologic malignancies

Fifteen patients with hematologic malignancies had potentially actionable findings, and 4 underwent treatment changes as a result. (None of the patients required genetic counseling.)

For a patient with pre-B acute lymphoblastic leukemia (ALL), sequencing revealed a homozygous CDKN2A deletion and an ETV6-ABL1 fusion. So the patient was placed on imatinib and had a sustained CR for 21 months.

A patient with early T-cell precursor ALL had a FLT3-ITD mutation, Chr16p gain, Chr16q loss, and FLT3 overexpression. The patient achieved a CR after transplant, was placed on the FLT3 inhibitor sorafenib, and remained in CR for 15 months.

Another patient with pre-B ALL had a FLT3 nonframeshift deletion and BLK and FLT3 overexpression. The patient was in CR for 9 months after a transplant and received sorafenib for 6 months.

A patient with biphenotypic leukemia had mutations in NRAS and PHF6; SPI1, ASXL1, and CBLC frameshift insertions; a JAK3-activating mutation; and JAK3 overexpression. The patient received the JAK3 inhibitor tofacitinib but could not tolerate the full dose and died of progressive disease.

Cost and turn-around time

The cost for sequencing was approximately $6000 per patient and was covered under the research protocol.

It took the researchers about 7 to 8 weeks to report the sequencing results back to treating physicians and families.

“These are early days, and the full promise of precision medicine is yet to be fully realized,” Dr Mody said. “We need better targeted therapies designed for children, and turnaround time for sequencing needs to be less than 2 weeks for it to be a regular part of a patient’s treatment plan.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Exome and transcriptome sequencing results can inform the management of young patients with relapsed, refractory, and rare malignancies, a new study suggests.

In a consecutive case series, sequencing data revealed potentially actionable findings for 46% of patients.

As a result, 15% of patients changed treatment, and 10% underwent genetic counseling.

Investigators described this research in JAMA.

“We found that, for some children with rare, difficult-to-treat, and aggressive cancers, this technology can dramatically change the course of their treatment,” said study author Rajen Mody, MBBS, of the University of Michigan in Ann Arbor.

Dr Mody and his colleagues evaluated 102 patients with relapsed, refractory, or rare cancers. Their median age was 11.5 (range, 0-22).

The patients underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing. Ninety-one patients (89%) had adequate tumor tissue to complete sequencing, including 28 patients (31%) with hematologic malignancies and 63 (69%) with solid tumors.

All sequencing results were discussed at a precision medicine tumor board, which included pediatric and adult oncologists, pathologists, genetics specialists, and other professionals. This group discussed the results and assessed the feasibility of pursuing treatment options based on the findings.

Actionable findings

Forty-two patients (46%) had potentially actionable findings, 15 (54%) with hematologic malignancies and 27 (43%) with solid tumors.

Actionable findings included a change in diagnosis (n=2), the presence of a genetic anomaly that could be targeted by an approved or experimental drug (n=31), and the need for genetic counseling for inherited cancer risk that could affect the patient or the whole family (n=9).

“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could potentially be higher over time,” said study author Arul Chinnaiyan, MD, PhD, also of the University of Michigan.

“These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis. If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient.”

Actions were taken in 23 of the 42 patients. Fourteen patients (15%) had their treatment changed, and 9 of these patients (10%) had durable partial or complete remissions (CRs) as a result.

Nine patients (10%) underwent genetic counseling because of sequencing results. The researchers noted that 4 of these patients had no notable family history to suggest an inherited risk, and they would not otherwise have been referred for genetic counseling.

Hematologic malignancies

Fifteen patients with hematologic malignancies had potentially actionable findings, and 4 underwent treatment changes as a result. (None of the patients required genetic counseling.)

For a patient with pre-B acute lymphoblastic leukemia (ALL), sequencing revealed a homozygous CDKN2A deletion and an ETV6-ABL1 fusion. So the patient was placed on imatinib and had a sustained CR for 21 months.

A patient with early T-cell precursor ALL had a FLT3-ITD mutation, Chr16p gain, Chr16q loss, and FLT3 overexpression. The patient achieved a CR after transplant, was placed on the FLT3 inhibitor sorafenib, and remained in CR for 15 months.

Another patient with pre-B ALL had a FLT3 nonframeshift deletion and BLK and FLT3 overexpression. The patient was in CR for 9 months after a transplant and received sorafenib for 6 months.

A patient with biphenotypic leukemia had mutations in NRAS and PHF6; SPI1, ASXL1, and CBLC frameshift insertions; a JAK3-activating mutation; and JAK3 overexpression. The patient received the JAK3 inhibitor tofacitinib but could not tolerate the full dose and died of progressive disease.

Cost and turn-around time

The cost for sequencing was approximately $6000 per patient and was covered under the research protocol.

It took the researchers about 7 to 8 weeks to report the sequencing results back to treating physicians and families.

“These are early days, and the full promise of precision medicine is yet to be fully realized,” Dr Mody said. “We need better targeted therapies designed for children, and turnaround time for sequencing needs to be less than 2 weeks for it to be a regular part of a patient’s treatment plan.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Exome and transcriptome sequencing results can inform the management of young patients with relapsed, refractory, and rare malignancies, a new study suggests.

In a consecutive case series, sequencing data revealed potentially actionable findings for 46% of patients.

As a result, 15% of patients changed treatment, and 10% underwent genetic counseling.

Investigators described this research in JAMA.

“We found that, for some children with rare, difficult-to-treat, and aggressive cancers, this technology can dramatically change the course of their treatment,” said study author Rajen Mody, MBBS, of the University of Michigan in Ann Arbor.

Dr Mody and his colleagues evaluated 102 patients with relapsed, refractory, or rare cancers. Their median age was 11.5 (range, 0-22).

The patients underwent integrative clinical exome (tumor and germline DNA) and transcriptome (tumor RNA) sequencing. Ninety-one patients (89%) had adequate tumor tissue to complete sequencing, including 28 patients (31%) with hematologic malignancies and 63 (69%) with solid tumors.

All sequencing results were discussed at a precision medicine tumor board, which included pediatric and adult oncologists, pathologists, genetics specialists, and other professionals. This group discussed the results and assessed the feasibility of pursuing treatment options based on the findings.

Actionable findings

Forty-two patients (46%) had potentially actionable findings, 15 (54%) with hematologic malignancies and 27 (43%) with solid tumors.

Actionable findings included a change in diagnosis (n=2), the presence of a genetic anomaly that could be targeted by an approved or experimental drug (n=31), and the need for genetic counseling for inherited cancer risk that could affect the patient or the whole family (n=9).

“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could potentially be higher over time,” said study author Arul Chinnaiyan, MD, PhD, also of the University of Michigan.

“These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis. If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient.”

Actions were taken in 23 of the 42 patients. Fourteen patients (15%) had their treatment changed, and 9 of these patients (10%) had durable partial or complete remissions (CRs) as a result.

Nine patients (10%) underwent genetic counseling because of sequencing results. The researchers noted that 4 of these patients had no notable family history to suggest an inherited risk, and they would not otherwise have been referred for genetic counseling.

Hematologic malignancies

Fifteen patients with hematologic malignancies had potentially actionable findings, and 4 underwent treatment changes as a result. (None of the patients required genetic counseling.)

For a patient with pre-B acute lymphoblastic leukemia (ALL), sequencing revealed a homozygous CDKN2A deletion and an ETV6-ABL1 fusion. So the patient was placed on imatinib and had a sustained CR for 21 months.

A patient with early T-cell precursor ALL had a FLT3-ITD mutation, Chr16p gain, Chr16q loss, and FLT3 overexpression. The patient achieved a CR after transplant, was placed on the FLT3 inhibitor sorafenib, and remained in CR for 15 months.

Another patient with pre-B ALL had a FLT3 nonframeshift deletion and BLK and FLT3 overexpression. The patient was in CR for 9 months after a transplant and received sorafenib for 6 months.

A patient with biphenotypic leukemia had mutations in NRAS and PHF6; SPI1, ASXL1, and CBLC frameshift insertions; a JAK3-activating mutation; and JAK3 overexpression. The patient received the JAK3 inhibitor tofacitinib but could not tolerate the full dose and died of progressive disease.

Cost and turn-around time

The cost for sequencing was approximately $6000 per patient and was covered under the research protocol.

It took the researchers about 7 to 8 weeks to report the sequencing results back to treating physicians and families.

“These are early days, and the full promise of precision medicine is yet to be fully realized,” Dr Mody said. “We need better targeted therapies designed for children, and turnaround time for sequencing needs to be less than 2 weeks for it to be a regular part of a patient’s treatment plan.”

Dendritic cells

Researchers believe they have discovered how therapy targeting CD47 harnesses the immune system to fight lymphoma and other cancers.

Conducting experiments in immune-competent mice, the team found that anti-CD47 therapy drives T-cell mediated elimination of lymphoma, colon cancer, and breast cancer.

The group’s research also revealed how the timing of chemotherapy administration affects anti-CD47 therapy.

Yang-Xin Fu, MD, PhD, of the University of Chicago in Illinois, and his colleagues described this research in Nature Medicine.

Previous research had shown that many cancer cells have CD47 on their surface. The protein instructs circulating macrophages not to devour the cells, but anti-CD47 therapy can negate this effect. This research relied on human tumors transplanted in immunocompromised mice.

With the current study, Dr Fu and his colleagues transplanted tumors from mice into genetically identical hosts with intact immune systems.

The team’s experiments revealed that anti-CD47-mediated tumor rejection requires both innate and adaptive immune responses. And the bulk of the therapeutic effect from CD47 blockade relies not on macrophages but on dendritic cells.

Dendritic cells proved more potent than macrophages at priming CD8⁺ T cells. Dendritic cells also caused type-1 interferon to boost adaptive immunity and activated the STING pathway, which was “absolutely essential for the antitumor effect of anti-CD47 therapy.”

The researchers also found evidence to suggest that chemotherapy should be administered before, rather than after, anti-CD47 therapy.

The team tested the anti-CD47 monoclonal antibody (mAb) MIAP301 in combination with clinically equivalent doses of cyclophosphamide or paclitaxel in mouse models of lymphoma (established A20 tumors).

When the chemotherapy was administered after the mAb, tumor regression was no faster than when the mAb was given alone.

In fact, the chemotherapy appeared to hinder antitumor memory responses generated by the mAb. When the researchers removed all tumors and rechallenged the mice with A20 cells, all of the mice that had received the mAb alone rejected the tumor rechallenge.

But mice that had received the mAb followed by chemotherapy were susceptible to tumor outgrowth—50% of cyclophosphamide-treated mice and 80% of paclitaxel-treated mice.

When chemotherapy was given before the mAb, however, it conferred benefits. A single dose of either chemotherapy drug synergized with the mAb to fight lymphoma.

And the treatment preserved the host memory response against relapsing tumors. All of the cyclophosphamide-treated mice and 80% of the paclitaxel-treated mice were resistant to tumor rechallenge.

The researchers said this suggests the order of treatment administration could have a major impact on primary and memory immune responses to tumors and alter outcomes of anti-CD47 therapy.

“Our results point to a new and more personalized strategy to modulate the tumor microenvironment,” Dr Fu said. “We think our approach, along with further investigation of scheduling and dosing, could improve survival and quality of life for patients battling advanced cancer.”

Dendritic cells

Researchers believe they have discovered how therapy targeting CD47 harnesses the immune system to fight lymphoma and other cancers.

Conducting experiments in immune-competent mice, the team found that anti-CD47 therapy drives T-cell mediated elimination of lymphoma, colon cancer, and breast cancer.

The group’s research also revealed how the timing of chemotherapy administration affects anti-CD47 therapy.

Yang-Xin Fu, MD, PhD, of the University of Chicago in Illinois, and his colleagues described this research in Nature Medicine.

Previous research had shown that many cancer cells have CD47 on their surface. The protein instructs circulating macrophages not to devour the cells, but anti-CD47 therapy can negate this effect. This research relied on human tumors transplanted in immunocompromised mice.

With the current study, Dr Fu and his colleagues transplanted tumors from mice into genetically identical hosts with intact immune systems.

The team’s experiments revealed that anti-CD47-mediated tumor rejection requires both innate and adaptive immune responses. And the bulk of the therapeutic effect from CD47 blockade relies not on macrophages but on dendritic cells.

Dendritic cells proved more potent than macrophages at priming CD8⁺ T cells. Dendritic cells also caused type-1 interferon to boost adaptive immunity and activated the STING pathway, which was “absolutely essential for the antitumor effect of anti-CD47 therapy.”

The researchers also found evidence to suggest that chemotherapy should be administered before, rather than after, anti-CD47 therapy.

The team tested the anti-CD47 monoclonal antibody (mAb) MIAP301 in combination with clinically equivalent doses of cyclophosphamide or paclitaxel in mouse models of lymphoma (established A20 tumors).

When the chemotherapy was administered after the mAb, tumor regression was no faster than when the mAb was given alone.

In fact, the chemotherapy appeared to hinder antitumor memory responses generated by the mAb. When the researchers removed all tumors and rechallenged the mice with A20 cells, all of the mice that had received the mAb alone rejected the tumor rechallenge.

But mice that had received the mAb followed by chemotherapy were susceptible to tumor outgrowth—50% of cyclophosphamide-treated mice and 80% of paclitaxel-treated mice.

When chemotherapy was given before the mAb, however, it conferred benefits. A single dose of either chemotherapy drug synergized with the mAb to fight lymphoma.

And the treatment preserved the host memory response against relapsing tumors. All of the cyclophosphamide-treated mice and 80% of the paclitaxel-treated mice were resistant to tumor rechallenge.

The researchers said this suggests the order of treatment administration could have a major impact on primary and memory immune responses to tumors and alter outcomes of anti-CD47 therapy.

“Our results point to a new and more personalized strategy to modulate the tumor microenvironment,” Dr Fu said. “We think our approach, along with further investigation of scheduling and dosing, could improve survival and quality of life for patients battling advanced cancer.”

Dendritic cells

Researchers believe they have discovered how therapy targeting CD47 harnesses the immune system to fight lymphoma and other cancers.

Conducting experiments in immune-competent mice, the team found that anti-CD47 therapy drives T-cell mediated elimination of lymphoma, colon cancer, and breast cancer.

The group’s research also revealed how the timing of chemotherapy administration affects anti-CD47 therapy.

Yang-Xin Fu, MD, PhD, of the University of Chicago in Illinois, and his colleagues described this research in Nature Medicine.

Previous research had shown that many cancer cells have CD47 on their surface. The protein instructs circulating macrophages not to devour the cells, but anti-CD47 therapy can negate this effect. This research relied on human tumors transplanted in immunocompromised mice.

With the current study, Dr Fu and his colleagues transplanted tumors from mice into genetically identical hosts with intact immune systems.

The team’s experiments revealed that anti-CD47-mediated tumor rejection requires both innate and adaptive immune responses. And the bulk of the therapeutic effect from CD47 blockade relies not on macrophages but on dendritic cells.

Dendritic cells proved more potent than macrophages at priming CD8⁺ T cells. Dendritic cells also caused type-1 interferon to boost adaptive immunity and activated the STING pathway, which was “absolutely essential for the antitumor effect of anti-CD47 therapy.”

The researchers also found evidence to suggest that chemotherapy should be administered before, rather than after, anti-CD47 therapy.

The team tested the anti-CD47 monoclonal antibody (mAb) MIAP301 in combination with clinically equivalent doses of cyclophosphamide or paclitaxel in mouse models of lymphoma (established A20 tumors).

When the chemotherapy was administered after the mAb, tumor regression was no faster than when the mAb was given alone.

In fact, the chemotherapy appeared to hinder antitumor memory responses generated by the mAb. When the researchers removed all tumors and rechallenged the mice with A20 cells, all of the mice that had received the mAb alone rejected the tumor rechallenge.

But mice that had received the mAb followed by chemotherapy were susceptible to tumor outgrowth—50% of cyclophosphamide-treated mice and 80% of paclitaxel-treated mice.

When chemotherapy was given before the mAb, however, it conferred benefits. A single dose of either chemotherapy drug synergized with the mAb to fight lymphoma.

And the treatment preserved the host memory response against relapsing tumors. All of the cyclophosphamide-treated mice and 80% of the paclitaxel-treated mice were resistant to tumor rechallenge.

The researchers said this suggests the order of treatment administration could have a major impact on primary and memory immune responses to tumors and alter outcomes of anti-CD47 therapy.

“Our results point to a new and more personalized strategy to modulate the tumor microenvironment,” Dr Fu said. “We think our approach, along with further investigation of scheduling and dosing, could improve survival and quality of life for patients battling advanced cancer.”

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Results of a new survey suggest many adults in the UK may be uninformed about cancer treatment options, despite broad media coverage of these therapies.

Personalized drug treatment, immunotherapy, and proton beam therapy have all been covered by the lay media and featured in news stories across the globe.

But a survey of more than 2000 UK adults showed that most respondents were not aware of these treatment types.

Only 19% of respondents said they had heard about immunotherapy, 29% had heard of personalized drug treatment, and 30% had heard of proton beam therapy.

The survey, which included 2081 adults, was conducted online by YouGov in June. It was commissioned by Cancer Research UK and other members of the Radiotherapy Awareness Programme.

The primary goal of the survey was to examine public awareness of radiotherapy. And the results showed that many respondents were unaware of newer, more targeted radiotherapy options.

Respondents were largely uninformed about other types of cancer treatment as well. However, of the respondents who elected to give their opinion (n=1877), most said the National Health Service (NHS) should fund chemotherapy and other drug treatments over radiotherapy.

Survey questions and responses were as follows.

Radiotherapy

Before taking this survey, which, if any, of the following types of radiotherapy had you heard of?

Other cancer treatments

Which, if any, of the following specific types of cancer treatments/tests had you heard of before taking this survey?

NHS funding

What level of priority do you think the NHS should give to funding each of the following 4 types of cancer treatments?

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Results of a new survey suggest many adults in the UK may be uninformed about cancer treatment options, despite broad media coverage of these therapies.

Personalized drug treatment, immunotherapy, and proton beam therapy have all been covered by the lay media and featured in news stories across the globe.

But a survey of more than 2000 UK adults showed that most respondents were not aware of these treatment types.

Only 19% of respondents said they had heard about immunotherapy, 29% had heard of personalized drug treatment, and 30% had heard of proton beam therapy.

The survey, which included 2081 adults, was conducted online by YouGov in June. It was commissioned by Cancer Research UK and other members of the Radiotherapy Awareness Programme.

The primary goal of the survey was to examine public awareness of radiotherapy. And the results showed that many respondents were unaware of newer, more targeted radiotherapy options.

Respondents were largely uninformed about other types of cancer treatment as well. However, of the respondents who elected to give their opinion (n=1877), most said the National Health Service (NHS) should fund chemotherapy and other drug treatments over radiotherapy.

Survey questions and responses were as follows.

Radiotherapy

Before taking this survey, which, if any, of the following types of radiotherapy had you heard of?

Other cancer treatments

Which, if any, of the following specific types of cancer treatments/tests had you heard of before taking this survey?

NHS funding

What level of priority do you think the NHS should give to funding each of the following 4 types of cancer treatments?

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Results of a new survey suggest many adults in the UK may be uninformed about cancer treatment options, despite broad media coverage of these therapies.

Personalized drug treatment, immunotherapy, and proton beam therapy have all been covered by the lay media and featured in news stories across the globe.

But a survey of more than 2000 UK adults showed that most respondents were not aware of these treatment types.

Only 19% of respondents said they had heard about immunotherapy, 29% had heard of personalized drug treatment, and 30% had heard of proton beam therapy.

The survey, which included 2081 adults, was conducted online by YouGov in June. It was commissioned by Cancer Research UK and other members of the Radiotherapy Awareness Programme.

The primary goal of the survey was to examine public awareness of radiotherapy. And the results showed that many respondents were unaware of newer, more targeted radiotherapy options.

Respondents were largely uninformed about other types of cancer treatment as well. However, of the respondents who elected to give their opinion (n=1877), most said the National Health Service (NHS) should fund chemotherapy and other drug treatments over radiotherapy.

Survey questions and responses were as follows.

Radiotherapy

Before taking this survey, which, if any, of the following types of radiotherapy had you heard of?

Other cancer treatments

Which, if any, of the following specific types of cancer treatments/tests had you heard of before taking this survey?

NHS funding

What level of priority do you think the NHS should give to funding each of the following 4 types of cancer treatments?

KHSV-infected cells (yellow)

Image courtesy of the

University of North Carolina

Researchers say they have uncovered a viral protein that inhibits cGAS, the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses.

The protein, Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity.

The team believes this finding could have a range of therapeutic implications.

“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, PhD, of Florida State University in Tallahassee.

Dr Zhu and his colleagues described this research in Cell Host and Microbe.

The authors noted that, although cGAS senses several DNA viruses, viral strategies targeting cGAS are “virtually unknown.”

To uncover a cGAS inhibitor, the researchers screened every protein in a KSHV cell—90 in total. This revealed KSHV ORF52, which the team renamed “KicGas,” an abbreviation for “KSHV inhibitor of cGAS.”

Further investigation revealed how KicGas inhibits cGAS activity: it must bind to both DNA and cGAS.

The researchers then found that ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA.

Finally, the team infected human cell lines with KSHV to mimic natural infection. They found that KSHV triggers a cGAS-dependent immune response that can be partially mitigated by KicGas.

When the researchers eliminated KicGas from infected cells, the cells produced a much stronger immune response.

For the next phase of research, the team is building a 3-dimensional model to help them better understand how KicGas functions. They hope this will help them utilize KicGas to fight disease.

KHSV-infected cells (yellow)

Image courtesy of the

University of North Carolina

Researchers say they have uncovered a viral protein that inhibits cGAS, the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses.

The protein, Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity.

The team believes this finding could have a range of therapeutic implications.

“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, PhD, of Florida State University in Tallahassee.

Dr Zhu and his colleagues described this research in Cell Host and Microbe.

The authors noted that, although cGAS senses several DNA viruses, viral strategies targeting cGAS are “virtually unknown.”

To uncover a cGAS inhibitor, the researchers screened every protein in a KSHV cell—90 in total. This revealed KSHV ORF52, which the team renamed “KicGas,” an abbreviation for “KSHV inhibitor of cGAS.”

Further investigation revealed how KicGas inhibits cGAS activity: it must bind to both DNA and cGAS.

The researchers then found that ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA.

Finally, the team infected human cell lines with KSHV to mimic natural infection. They found that KSHV triggers a cGAS-dependent immune response that can be partially mitigated by KicGas.

When the researchers eliminated KicGas from infected cells, the cells produced a much stronger immune response.

For the next phase of research, the team is building a 3-dimensional model to help them better understand how KicGas functions. They hope this will help them utilize KicGas to fight disease.

KHSV-infected cells (yellow)

Image courtesy of the

University of North Carolina

Researchers say they have uncovered a viral protein that inhibits cGAS, the principal cytosolic DNA sensor that detects invading viral DNA and triggers antiviral responses.

The protein, Kaposi’s sarcoma-associated herpesvirus (KSHV) ORF52, subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity.

The team believes this finding could have a range of therapeutic implications.

“We can manipulate the protein and/or the sensor to boost or tune down the immune response in order to fight infectious and autoimmune diseases, as well as cancers,” said Fanxiu Zhu, PhD, of Florida State University in Tallahassee.

Dr Zhu and his colleagues described this research in Cell Host and Microbe.

The authors noted that, although cGAS senses several DNA viruses, viral strategies targeting cGAS are “virtually unknown.”

To uncover a cGAS inhibitor, the researchers screened every protein in a KSHV cell—90 in total. This revealed KSHV ORF52, which the team renamed “KicGas,” an abbreviation for “KSHV inhibitor of cGAS.”

Further investigation revealed how KicGas inhibits cGAS activity: it must bind to both DNA and cGAS.

The researchers then found that ORF52 homologs in other gammaherpesviruses also inhibit cGAS activity and similarly bind cGAS and DNA.

Finally, the team infected human cell lines with KSHV to mimic natural infection. They found that KSHV triggers a cGAS-dependent immune response that can be partially mitigated by KicGas.

When the researchers eliminated KicGas from infected cells, the cells produced a much stronger immune response.

For the next phase of research, the team is building a 3-dimensional model to help them better understand how KicGas functions. They hope this will help them utilize KicGas to fight disease.

DNA coiled around histones

Image by Eric Smith

Researchers say they have discovered critical details that explain how a cellular response system tells the difference between damage to the body’s own DNA and the foreign DNA of an invading virus.

The team believes this discovery could aid the development of new cancer-selective viral therapies, and it may help explain why aging, cancers, and other diseases

seem to open the door to viral infections.

“Our study reveals fundamental mechanisms that distinguish DNA breaks at cellular and viral genomes to trigger different responses that protect the host,” said Clodagh O’Shea, of the Salk Institute for Biological Studies in La Jolla, California.

“The findings may also explain why certain conditions like aging, cancer chemotherapy, and inflammation make us more susceptible to viral infection.”

Dr O’Shea and Govind Shah, PhD, also of the Salk Institute, reported these findings in Cell.

The pair described how a cluster of proteins known as the MRN complex detects DNA breaks and amplifies its response through histones.

MRN starts a domino effect, activating histones on surrounding chromosomes, which summons a cascade of additional proteins and results in a cell-wide, all-hands-on-deck alarm to help mend the DNA.

If the cell can’t fix the DNA break, it will induce apoptosis—a self-destruct mechanism that helps to prevent mutated cells from replicating and therefore prevents tumor growth.

“What’s interesting is that even a single break transmits a global signal through the cell, halting cell division and growth,” Dr O’Shea said. “This response prevents replication so the cell doesn’t pass on a break.”

Drs O’Shea and Shah also found that, when it comes to defending against DNA viruses, the cell’s response system begins the same way—with MRN detecting breaks. But it never progresses to the global alarm signal in the case of the virus.

Typically, a common DNA virus enters the cell’s nucleus and turns on genes to replicate its own DNA. The cell detects the unauthorized replication, and the MRN complex grabs and selectively neutralizes viral DNA without triggering a global response that would arrest or kill the cell.

So the MRN response to the virus stays localized and only selectively prevents viral, but not cellular, replication.

When both threats to the genome are present, MRN will activate the massive response at the DNA break, and no MRN is left to respond to the virus. This means the virus is effectively ignored while the cell responds to the more massive alarm.

“The requirement of MRN for sensing both cellular and viral genome breaks has profound consequences,” Dr O’Shea said.

“When MRN is recruited to cellular DNA breaks, it can no longer sense and respond to incoming viral genomes. Thus, the act of responding to cellular genome breaks inactivates the host’s defenses to viral replication.”

Dr O’Shea said this may explain why people who have high levels of cellular DNA damage—such as cancer patients—are more susceptible to viral infections.

“Having damaged DNA compromises our cells’ ability to fight viral infection, while having healthy DNA boosts our cells’ ability to catch viral DNA,” Dr Shah said. “Our work implies that we may be able to engineer viruses that selectively kill cancer cells.”

The researchers aim to use this new knowledge to create viruses that are destroyed in normal cells but replicate specifically in cancer cells.

Unlike normal cells, cancer cells almost always have very high levels of DNA damage. In cancer cells, MRN is already so preoccupied with responding to DNA breaks that an engineered virus could sneak in undetected.

“Cancer cells, by definition, have high mutation rates and genomic instability even at the very earliest stages,” Dr O’Shea said. “So you could imagine building a virus that could destroy even the earliest lesions and be used as a prophylactic.”

DNA coiled around histones

Image by Eric Smith

Researchers say they have discovered critical details that explain how a cellular response system tells the difference between damage to the body’s own DNA and the foreign DNA of an invading virus.

The team believes this discovery could aid the development of new cancer-selective viral therapies, and it may help explain why aging, cancers, and other diseases

seem to open the door to viral infections.

“Our study reveals fundamental mechanisms that distinguish DNA breaks at cellular and viral genomes to trigger different responses that protect the host,” said Clodagh O’Shea, of the Salk Institute for Biological Studies in La Jolla, California.

“The findings may also explain why certain conditions like aging, cancer chemotherapy, and inflammation make us more susceptible to viral infection.”

Dr O’Shea and Govind Shah, PhD, also of the Salk Institute, reported these findings in Cell.

The pair described how a cluster of proteins known as the MRN complex detects DNA breaks and amplifies its response through histones.

MRN starts a domino effect, activating histones on surrounding chromosomes, which summons a cascade of additional proteins and results in a cell-wide, all-hands-on-deck alarm to help mend the DNA.

If the cell can’t fix the DNA break, it will induce apoptosis—a self-destruct mechanism that helps to prevent mutated cells from replicating and therefore prevents tumor growth.

“What’s interesting is that even a single break transmits a global signal through the cell, halting cell division and growth,” Dr O’Shea said. “This response prevents replication so the cell doesn’t pass on a break.”

Drs O’Shea and Shah also found that, when it comes to defending against DNA viruses, the cell’s response system begins the same way—with MRN detecting breaks. But it never progresses to the global alarm signal in the case of the virus.

Typically, a common DNA virus enters the cell’s nucleus and turns on genes to replicate its own DNA. The cell detects the unauthorized replication, and the MRN complex grabs and selectively neutralizes viral DNA without triggering a global response that would arrest or kill the cell.

So the MRN response to the virus stays localized and only selectively prevents viral, but not cellular, replication.

When both threats to the genome are present, MRN will activate the massive response at the DNA break, and no MRN is left to respond to the virus. This means the virus is effectively ignored while the cell responds to the more massive alarm.

“The requirement of MRN for sensing both cellular and viral genome breaks has profound consequences,” Dr O’Shea said.

“When MRN is recruited to cellular DNA breaks, it can no longer sense and respond to incoming viral genomes. Thus, the act of responding to cellular genome breaks inactivates the host’s defenses to viral replication.”

Dr O’Shea said this may explain why people who have high levels of cellular DNA damage—such as cancer patients—are more susceptible to viral infections.

“Having damaged DNA compromises our cells’ ability to fight viral infection, while having healthy DNA boosts our cells’ ability to catch viral DNA,” Dr Shah said. “Our work implies that we may be able to engineer viruses that selectively kill cancer cells.”

The researchers aim to use this new knowledge to create viruses that are destroyed in normal cells but replicate specifically in cancer cells.

Unlike normal cells, cancer cells almost always have very high levels of DNA damage. In cancer cells, MRN is already so preoccupied with responding to DNA breaks that an engineered virus could sneak in undetected.

“Cancer cells, by definition, have high mutation rates and genomic instability even at the very earliest stages,” Dr O’Shea said. “So you could imagine building a virus that could destroy even the earliest lesions and be used as a prophylactic.”

DNA coiled around histones

Image by Eric Smith

Researchers say they have discovered critical details that explain how a cellular response system tells the difference between damage to the body’s own DNA and the foreign DNA of an invading virus.

The team believes this discovery could aid the development of new cancer-selective viral therapies, and it may help explain why aging, cancers, and other diseases

seem to open the door to viral infections.

“Our study reveals fundamental mechanisms that distinguish DNA breaks at cellular and viral genomes to trigger different responses that protect the host,” said Clodagh O’Shea, of the Salk Institute for Biological Studies in La Jolla, California.

“The findings may also explain why certain conditions like aging, cancer chemotherapy, and inflammation make us more susceptible to viral infection.”

Dr O’Shea and Govind Shah, PhD, also of the Salk Institute, reported these findings in Cell.

The pair described how a cluster of proteins known as the MRN complex detects DNA breaks and amplifies its response through histones.

MRN starts a domino effect, activating histones on surrounding chromosomes, which summons a cascade of additional proteins and results in a cell-wide, all-hands-on-deck alarm to help mend the DNA.

If the cell can’t fix the DNA break, it will induce apoptosis—a self-destruct mechanism that helps to prevent mutated cells from replicating and therefore prevents tumor growth.

“What’s interesting is that even a single break transmits a global signal through the cell, halting cell division and growth,” Dr O’Shea said. “This response prevents replication so the cell doesn’t pass on a break.”

Drs O’Shea and Shah also found that, when it comes to defending against DNA viruses, the cell’s response system begins the same way—with MRN detecting breaks. But it never progresses to the global alarm signal in the case of the virus.

Typically, a common DNA virus enters the cell’s nucleus and turns on genes to replicate its own DNA. The cell detects the unauthorized replication, and the MRN complex grabs and selectively neutralizes viral DNA without triggering a global response that would arrest or kill the cell.

So the MRN response to the virus stays localized and only selectively prevents viral, but not cellular, replication.

When both threats to the genome are present, MRN will activate the massive response at the DNA break, and no MRN is left to respond to the virus. This means the virus is effectively ignored while the cell responds to the more massive alarm.

“The requirement of MRN for sensing both cellular and viral genome breaks has profound consequences,” Dr O’Shea said.

“When MRN is recruited to cellular DNA breaks, it can no longer sense and respond to incoming viral genomes. Thus, the act of responding to cellular genome breaks inactivates the host’s defenses to viral replication.”

Dr O’Shea said this may explain why people who have high levels of cellular DNA damage—such as cancer patients—are more susceptible to viral infections.

“Having damaged DNA compromises our cells’ ability to fight viral infection, while having healthy DNA boosts our cells’ ability to catch viral DNA,” Dr Shah said. “Our work implies that we may be able to engineer viruses that selectively kill cancer cells.”

The researchers aim to use this new knowledge to create viruses that are destroyed in normal cells but replicate specifically in cancer cells.

Unlike normal cells, cancer cells almost always have very high levels of DNA damage. In cancer cells, MRN is already so preoccupied with responding to DNA breaks that an engineered virus could sneak in undetected.

“Cancer cells, by definition, have high mutation rates and genomic instability even at the very earliest stages,” Dr O’Shea said. “So you could imagine building a virus that could destroy even the earliest lesions and be used as a prophylactic.”

Patient consults pharmacist

Photo by Rhoda Baer

A new study suggests that seniors with cancer may be taking complementary or alternative medicines (CAMs) without their oncologists’ knowledge.

In this single-center study, 27% of senior cancer patients took CAMs at some point during their cancer care.

CAM usage was highest among patients ages 80 to 89, women, Caucasians, and patients with solid tumor malignancies.

Polypharmacy and certain comorbidities were linked to CAM use as well.

Researchers reported these findings in the Journal of Geriatric Oncology.

“Currently, few oncologists are aware of the alternative medicines their patients take,” said study author Ginah Nightingale, PharmD, of Thomas Jefferson University in Philadelphia, Pennsylvania.

“Patients often fail to disclose the CAMs they take because they think they are safe, natural, nontoxic, and not relevant to their cancer care; because they think their doctor will disapprove; or because the doctor doesn’t specifically ask.”

To quantify CAM use in older cancer patients treated at their institution, Dr Nightingale and her colleagues surveyed patients who came to the Senior Adult Oncology Center at Thomas Jefferson University.

In a single visit, patients were seen by a medical oncologist, geriatrician, clinical pharmacist, social worker, and dietician. As part of this assessment, the patients brought in the contents of their medicine cabinets, and the medications they actively used were reviewed and recorded.

A total of 234 patients were included in the final analysis. Their mean age was 79.9 (range, 61–98). Most (87%) had solid tumor malignancies, were Caucasian (74%), and were female (64%).

In all, 26.5% of patients (n=62) had taken at least 1 CAM during their cancer care, with 19.2% taking 1 CAM, 6.4% taking 2, 0.4% taking 3, and 0.4% taking 4 or more CAMs. The highest number of CAMs taken was 10.

CAM usage was highest among patients ages 80 to 89, women, Caucasians, and patients with solid tumor malignancies.

Comorbidities significantly associated with CAM use were vision impairment (P=0.048) and urologic comorbidities (P=0.021). Polypharmacy (concurrent use of 5 or more medications) was significantly associated with CAM use as well (P=0.045).

Some of the commonly used CAMs were mega-dose vitamins or minerals, as well as treatments for macular degeneration, stomach probiotics, and joint health.

The researchers did not examine the potential adverse effects of these medications, but Dr Nightingale said some are known to have a biochemical effect on the body and other drugs.

“It is very important to do a comprehensive screen of all of the medications that older cancer patients take, including CAMs,” she added. “Clear and transparent documentation of CAM use should be recorded in the patient’s medical record. This documentation should indicate that patient-specific communication and/or education was provided so that shared and informed decisions by the patient can be made regarding the continued use of these medications.”

Patient consults pharmacist

Photo by Rhoda Baer

A new study suggests that seniors with cancer may be taking complementary or alternative medicines (CAMs) without their oncologists’ knowledge.

In this single-center study, 27% of senior cancer patients took CAMs at some point during their cancer care.

CAM usage was highest among patients ages 80 to 89, women, Caucasians, and patients with solid tumor malignancies.

Polypharmacy and certain comorbidities were linked to CAM use as well.

Researchers reported these findings in the Journal of Geriatric Oncology.

“Currently, few oncologists are aware of the alternative medicines their patients take,” said study author Ginah Nightingale, PharmD, of Thomas Jefferson University in Philadelphia, Pennsylvania.

“Patients often fail to disclose the CAMs they take because they think they are safe, natural, nontoxic, and not relevant to their cancer care; because they think their doctor will disapprove; or because the doctor doesn’t specifically ask.”

To quantify CAM use in older cancer patients treated at their institution, Dr Nightingale and her colleagues surveyed patients who came to the Senior Adult Oncology Center at Thomas Jefferson University.

In a single visit, patients were seen by a medical oncologist, geriatrician, clinical pharmacist, social worker, and dietician. As part of this assessment, the patients brought in the contents of their medicine cabinets, and the medications they actively used were reviewed and recorded.

A total of 234 patients were included in the final analysis. Their mean age was 79.9 (range, 61–98). Most (87%) had solid tumor malignancies, were Caucasian (74%), and were female (64%).

In all, 26.5% of patients (n=62) had taken at least 1 CAM during their cancer care, with 19.2% taking 1 CAM, 6.4% taking 2, 0.4% taking 3, and 0.4% taking 4 or more CAMs. The highest number of CAMs taken was 10.

CAM usage was highest among patients ages 80 to 89, women, Caucasians, and patients with solid tumor malignancies.

Comorbidities significantly associated with CAM use were vision impairment (P=0.048) and urologic comorbidities (P=0.021). Polypharmacy (concurrent use of 5 or more medications) was significantly associated with CAM use as well (P=0.045).

Some of the commonly used CAMs were mega-dose vitamins or minerals, as well as treatments for macular degeneration, stomach probiotics, and joint health.

The researchers did not examine the potential adverse effects of these medications, but Dr Nightingale said some are known to have a biochemical effect on the body and other drugs.

“It is very important to do a comprehensive screen of all of the medications that older cancer patients take, including CAMs,” she added. “Clear and transparent documentation of CAM use should be recorded in the patient’s medical record. This documentation should indicate that patient-specific communication and/or education was provided so that shared and informed decisions by the patient can be made regarding the continued use of these medications.”

Patient consults pharmacist

Photo by Rhoda Baer

A new study suggests that seniors with cancer may be taking complementary or alternative medicines (CAMs) without their oncologists’ knowledge.

In this single-center study, 27% of senior cancer patients took CAMs at some point during their cancer care.

CAM usage was highest among patients ages 80 to 89, women, Caucasians, and patients with solid tumor malignancies.

Polypharmacy and certain comorbidities were linked to CAM use as well.

Researchers reported these findings in the Journal of Geriatric Oncology.

“Currently, few oncologists are aware of the alternative medicines their patients take,” said study author Ginah Nightingale, PharmD, of Thomas Jefferson University in Philadelphia, Pennsylvania.

“Patients often fail to disclose the CAMs they take because they think they are safe, natural, nontoxic, and not relevant to their cancer care; because they think their doctor will disapprove; or because the doctor doesn’t specifically ask.”

To quantify CAM use in older cancer patients treated at their institution, Dr Nightingale and her colleagues surveyed patients who came to the Senior Adult Oncology Center at Thomas Jefferson University.

In a single visit, patients were seen by a medical oncologist, geriatrician, clinical pharmacist, social worker, and dietician. As part of this assessment, the patients brought in the contents of their medicine cabinets, and the medications they actively used were reviewed and recorded.

A total of 234 patients were included in the final analysis. Their mean age was 79.9 (range, 61–98). Most (87%) had solid tumor malignancies, were Caucasian (74%), and were female (64%).

In all, 26.5% of patients (n=62) had taken at least 1 CAM during their cancer care, with 19.2% taking 1 CAM, 6.4% taking 2, 0.4% taking 3, and 0.4% taking 4 or more CAMs. The highest number of CAMs taken was 10.

CAM usage was highest among patients ages 80 to 89, women, Caucasians, and patients with solid tumor malignancies.

Comorbidities significantly associated with CAM use were vision impairment (P=0.048) and urologic comorbidities (P=0.021). Polypharmacy (concurrent use of 5 or more medications) was significantly associated with CAM use as well (P=0.045).

Some of the commonly used CAMs were mega-dose vitamins or minerals, as well as treatments for macular degeneration, stomach probiotics, and joint health.

The researchers did not examine the potential adverse effects of these medications, but Dr Nightingale said some are known to have a biochemical effect on the body and other drugs.

“It is very important to do a comprehensive screen of all of the medications that older cancer patients take, including CAMs,” she added. “Clear and transparent documentation of CAM use should be recorded in the patient’s medical record. This documentation should indicate that patient-specific communication and/or education was provided so that shared and informed decisions by the patient can be made regarding the continued use of these medications.”