“The use of drugs that target genetic mutations driving the growth of tumors has revolutionized treatment for several serious forms of cancer, but in almost every case, tumors become resistant to the drugs’ therapeutic effects and resume growth, often through the emergence of new mutations, which has spurred the development of more powerful drugs that can overcome resistance mutations. In the Dec. 24 issue of New England Journal of Medicine, Massachusetts General Hospital (MGH) physicians report their study examining the evolution of drug resistance in a lung cancer patient treated with multiple different targeted therapies. When resistance developed to the third targeted therapy, the new mutation actually restored the cancer’s response to the very first targeted therapy drug used to treat the patient.”
“Dan Woska was weighing his treatment options after he was found to have prostate cancer two years ago when a friend mentioned a new genomic test that could gauge how lethal his tumor was.
“The test, called Oncotype DX, which looks at the expression of 17 genes in a tumor, cost about $4,000 and was not covered by Mr. Woska’s insurance. But through a patient assistance program, the company that created it, Genomic Health, ran it for him free, using a tiny grain of tissue left over from his biopsy. The results indicated there was an 81 percent probability that Mr. Woska’s tumor would not spread beyond the prostate. On an aggressiveness scale of zero to 100, the tumor was an indolent 15.
“Thrilled and relieved, Mr. Woska decided to forgo radiation and surgery.”
“Scientists have developed a blood test that can identify key mutations driving resistance to a widely used prostate cancer drug, and identify in advance patients who will not respond to treatment.
“The new research paves the way for information from a blood test to inform prostate cancer treatment in future, with only those patients whose cancers are free of resistance mutations taking the drug, abiraterone.
“The study is also a proof of principle that tests for cancer DNA in the bloodstream can be used to detect drug resistance mutations – allowing patients who will not benefit from one drug to be given an alternative treatment instead.
“Researchers at The Institute of Cancer Research, London, the Royal Marsden NHS Foundation Trust, and the University of Trento, Italy, analysed 274 blood samples from 97 patients using state-of-the-art DNA sequencing techniques.
“They found that mutations in a gene called the androgen receptor (AR) predicted resistance to the prostate cancer drug abiraterone, and that patients with these mutations had poorer survival.”
Women diagnosed with localized breast cancer face difficult decisions with their doctors. What kind of neoadjuvant (before surgery) treatment to choose? Should chemotherapy follow surgery? Based on the subtype of breast cancer, should specific chemotherapy drugs be used? Continue reading…
“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.”
“The ECOG-ACRIN Cancer Research Group has opened the largest precision medicine cancer trial to date.
“The phase 2 National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial will evaluate the efficacy of targeted therapies in patients whose tumors share specific gene abnormalities. Treatment choice will be made based on these abnormalities rather than the site of origin of the malignancy.
“ ‘The primary underpinning of the trial comes from genetic characterization of various cancer types, which has become increasingly common place but is not yet routine,’ Keith T. Flaherty, MD, an oncologist at Massachusetts General Hospital, associate professor at Harvard Medical School andECOG-ACRIN chair of the NCI-MATCH trial, told HemOnc Today. ‘When looking at cancers as defined by their site of origin, there are threads of continuity across those cancer types. Within a cancer type, there also is heterogeneity, and understanding what this patchwork looks like was really the main motivator for setting up a trial like this.’ “
“Immunotherapy has received a boost as a treatment approach for cancer, in light of research carried out by a group of international scientists led by a team at the University of California-San Francisco.
“Moreover, it seems likely that one of these mutations may be specifically involved in shielding new DM tumors from destruction by the immune system.
“DM is different in formation and appearance from other melanomas. It develops slowly and is unpigmented and scar-like in appearance. A tingling sensation may occur as it grows into nerves.”
“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.”
“In an analysis reported in the Journal of Clinical Oncology, Meric-Bernstam and colleagues at The University of Texas MD Anderson Cancer Center found that a small minority of patients with potentially actionable genes identified in large-scale testing were enrolled onto clinical trials targeting the alterations.
“The study included 2,000 consecutive patients with advanced cancer who underwent testing in a genomic testing protocol. Standardized hotspot mutation analysis was performed using either an 11-gene (251 patients) or a 46- or 50-gene (1,749 patients) multiplex platform. A total of 35 genes were considered potentially actionable, given the potential to be targeted with approved or investigational therapies.
“In total, 789 patients (39%) had at least one mutation in potentially actionable genes. Of them, 83 (11%) were enrolled in genotype-matched trials targeting these alterations. Among 230 patients with PIK3CA/AKT1/PTEN/BRAF mutations who returned for therapy, 116 (50%) received a genotype-matched drug; of them, 40 (17%) were treated in a genotype-selected trial requiring a mutation for eligibility, 16 (7%) were treated in a genotype-relevant trial targeting a genomic alteration without biomarker selection, and 40 (17%) received a genotype-relevant drug off trial.”