More Cancer Mutations May Be Good for Immunotherapy Patients

Excerpt:

“Mark Perkins considers himself a poster child for the new generation of cancer drugs that harness the patient’s immune system to attack sick cells. Two years after trying Merck & Co.’s Keytruda — and almost four years after receiving a prognosis of as little as six months left to live — he is cancer free.

“The 56-year-old grandfather’s case is more than a success story for a new class of treatments that have fewer side effects than standard chemotherapy. It’s also at the frontier of what could possibly lead to a new approach to treating cancer, if it turns out that patients who, like Perkins, have many more mutations in their tumors than the average have a better chance of responding to immunotherapy.

“Drugs like Keytruda, known as checkpoint inhibitors, have produced dramatic responses in some advanced cancer patients, but doctors still don’t understand why only about 20 percent gain long-term survival. Researchers say looking at the mutation load for answers makes scientific sense, because these drugs work by taking the brakes off the immune system’s killer T-cells, unleashing them to go after cancerous cells. In theory, the more mutations a cancer has, the more foreign it will appear to the newly enhanced immune cells.”

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Healthy People Can Now Order a $299 'Liquid Biopsy' Blood Test for Cancer. Should You Get It?

“The way we find cancer in our bodies today is often messy, imprecise and even potentially dangerous. It often involves taking sometimes fuzzy, unreadable images with CTs, MRIs and X-ray machines and cutting open our bodies to harvest bits of tissue for further analysis.

“Most of us never think to undergo such testing until it’s too late, and the cancer has already well on its way to killing us.

“A California-based company called Pathway Genomics is aiming to shake up this way of thinking about cancer detection. In September, Pathway announced that it would be offering an ‘early warning’ test that it says can detect snippets of abnormal DNA — for a whole group of major cancers, including breast, ovarian, lung, thyroid and prostate — in otherwise healthy people from a single vial of blood.”


Mutation Status Guides Advanced NSCLC Therapy

“The presence or absence of mutations in advanced non-small cell lung cancer (NSCLC) should guide selection of first-line systemic therapy, according to an updated clinical guideline from the American Society of Clinical Oncology.

“Patients with squamous-cell tumors that have no gene alterations should begin treatment with combination platinum-based cytotoxic chemotherapy, so long as they have good performance status (0 or 1). Optionally, bevacizumab (Avastin) may be added when the platinum agent is carboplatin. For patients with performance status 2, either chemotherapy or palliative care alone is an acceptable option.

“In the presence of sensitizing EGFR mutations, appropriate first-line therapy is afatinib (Gilotrif), erlotinib (Tarceva), or gefitinib (Iressa). Treatment should begin with crizotinib (Xalkori) when patients have tumors with ALK or ROS1 rearrangements, as published online in the Journal of Clinical Oncology.”


Predicting Prostate Cancer: Test Identifies New Methods for Treatment

“A genetic discovery out of the University of Pittsburgh School of Medicine is leading to a highly accurate test for aggressive prostate cancer and identifies new avenues for treatment.

“The analysis, published today in the American Journal of Pathology, found that prostate cancer patients who carry certain genetic mutations have a 91 percent chance of their cancer recurring. This research was funded by the National Institutes of Health (NIH), American Cancer Society and University of Pittsburgh Cancer Institute (UPCI).

” ‘Being able to say, with such certainty, that a patient is nearly guaranteed to see a recurrence of his prostate cancer means that doctors and patients can elect to be more aggressive in treating the cancer, knowing that the benefits likely outweigh the risks,’ said Jian-Hua Luo, M.D., Ph.D., professor of pathology, Pitt School of Medicine and member of UPCI. ‘Eventually, this could lead to a cure for prostate cancer through genetic therapy. With this discovery, we’re at the tip of the iceberg in terms of possibilities for improving patient outcomes.’ “


BRCA2 Mutations Herald Poor Prognosis in Screen-Detected Prostate Cancer

Editor’s note: You may have heard about the BRCA2 mutation, which can increase a person’s risk for breast cancer. Studies have also shown that it can increase a man’s risk of prostate cancer. Studies have also shown that prostate cancer patients with BRCA2 mutations generally do not survive as long as prostate cancer patients without BRCA2 mutations. A new study explored this more in depth by looking at survival rates for BRCA2+ men who were diagnosed with prostate cancer after standard screening. These men did indeed have shorter survival times than prostate cancer patients without BRCA2 mutations. The researchers say these patients might “benefit from additional therapies, such as with cis-platinum or a PARP [poly ADP-ribose polymerase] inhibitor.”

“Among men with prostate cancer detected on screening, survival among those with a mutation in the BRCA2 gene is much poorer than in those without such a mutation, researchers report.

“The findings suggest that BRCA2 mutation carriers may warrant additional treatments to improve their prognosis, say Steven Narod (Women’s College Hospital, Toronto, Ontario) and fellow authors writing in the British Journal of Cancer.

“BRCA2 mutations are known to confer an increased risk for developing prostate cancer and also to be associated with more aggressive tumours. However, the effect of BRCA2 mutations status on mortality in the setting of screen-detected cancers is unclear.”


UPDATE 1-Roche Skin Cancer Drug Meets Main Goal in Combination Study

“An experimental drug from Roche helped people with an advanced form of skin cancer live longer without their disease worsening when used in combination with another treatment, the Swiss drugmaker said on Monday.

“Pharmaceutical companies are looking to combination therapy to yield better results and drug cocktails are expected to be crucial as oncologists seek to block cancer on multiple fronts.

“Cobimetinib, which is being developed in collaboration with Exelixis Inc, is designed to be used with another Roche drug called Zelboraf for patients with tumors that have a mutation in a gene known as BRAF that allows melanoma cells to grow.”

Editor’s note: Cobimetinib is meant to be used in combination with the targeted therapy Zelboraf (vemurafenib) to treat people with melanoma whose tumors have a mutation in the BRAF gene. Oncologists can use a method called molecular testing to figure out whether a patient has a BRAF mutation.


Gene Mutation May Lead to Treatment for Liver Cancer

Editor’s note: Cancer is caused by genetic mutations that lead to excess cell growth and tumor formation. Scientists have identified many specific cancer-causing mutations, and drugs have been developed to target and treat tumors with some of these specific mutations. Researchers recently discovered that two mutations—IDH1 and IDH2—can lead to the development of intrahepatic cholangiocarcinoma (iCCA). The discovery could open up new treatment options for some patients who have these mutations. Indeed, there are ongoing clinical trials testing new drugs in patients with IDH1 and IDH2 mutations.

“Two genetic mutations in liver cells may drive tumor formation in intrahepatic cholangiocarcinoma (iCCA), the second most common form of liver cancer, according to a research published in the July issue of the journal Nature.

“A team led by the Icahn School of Medicine at Mount Sinai and Harvard Medical School has discovered a link between the presence of two mutant proteins IDH1 and IDH2 and cancer. Past studies have found IDH mutations to be among the most common genetic differences seen in patients with iCCA, but how they contribute to cancer development was unknown going into the current effort.

“iCCA strikes bile ducts, tube-like structures in the liver that carry bile, which is required for the digestion of food. With so much still unknown about the disease, there is no first-line, standard of care and no successful therapies.

” ‘iCCA is resistant to standard treatments like chemotherapy and radiation,’ said Josep Maria Llovet, MD, Director of the Liver Cancer Program, Division of Medicine, Icahn School of Medicine at Mount Sinai, and contributing author. ‘Understanding the molecular mechanism of the disease is the key to finding a treatment that works.’ ”


Study Identifies Novel Genomic Changes in the Most Common Type of Lung Cancer; TCGA Finds Mutations in a Key Cancer-Causing Pathway, Expanding Targets for Existing Drugs

Editor’s note: Cancer is caused by genetic mutations that lead to excess cell growth and tumor formation. Scientists have identified many specific cancer-causing mutations, and drugs have been developed to target and treat tumors with some of these specific mutations. Researchers recently found mutations in lung adenocarcinoma tumors that they had not seen in that type of cancer before. The discovery could eventually lead to new treatment options for some patients who have these mutations.

“Researchers from The Cancer Genome Atlas (TCGA) Research Network have identified novel mutations in a well-known cancer-causing pathway in lung adenocarcinoma, the most common subtype of lung cancer. Knowledge of these genomic changes may expand the number of possible therapeutic targets for this disease and potentially identify a greater number of patients with treatable mutations because many potent cancer drugs that target these mutations already exist.

“TCGA is jointly funded and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health. A TCGA analysis of another, less common, form of lung cancer, squamous cell carcinoma, was reported in 2012.

“In this new study, published online July 9, 2014, in the journal Nature, researchers examined the genomes, RNA, and some protein from 230 lung adenocarcinoma samples. In three-quarters of the samples, the scientists ultimately identified mutations that put a cell signaling pathway known as the RTK/RAS/RAF pathway into overdrive.”


Mayo Clinic Recommends New Routine Testing for some Non-Hodgkin Lymphomas

Editor’s note: Testing a patient’s tumors for mutated genes can give doctors important information about that patient’s outlook and appropriate treatments. This article discusses two predictive mutations that doctors can test for in the tumors of people with anaplastic large-cell lymphoma (ALCL) who have already been found not to have a mutation in the ALK gene.

Excerpt:

“A Mayo Clinic-led group of researchers has discovered three subgroups of a single type of non-Hodgkin lymphoma that have markedly different survival rates. These subgroups could not be differentiated by routine pathology but only with the aid of novel genetic tests, which the research team recommends giving to all patients with ALK-negative anaplastic large-cell lymphoma (ALCL). Findings are published in the journal Blood.

“Patients whose lymphomas had TP63 rearrangements had only a 17 percent chance of living five years beyond diagnosis, compared to 90 percent of patients whose tumors had DUSP22 rearrangements. A third group of tumors, those with neither rearrangement, was associated with an intermediate survival rate.

“ ‘This is the first study to demonstrate unequivocal genetic and clinical heterogeneity among systemic ALK-negative anaplastic large-cell lymphomas,’ says Andrew L. Feldman, M.D., a Mayo Clinic pathologist and senior author on the multi-institutional study. ‘Most strikingly, patients with DUSP22-rearranged ALCL had excellent overall survival rates, while patients with TP63-rearranged ALCL had dismal outcomes and nearly always failed standard therapy.’ Dr. Feldman also is a Damon Runyon Clinical Investigator.”