“A decade ago, researchers believed molecular alterations occurred in only one or two cancer types. That way of thinking has changed, however, with the understanding that the same alterations, especially gene fusions, can occur across many different tumor types.
“As a result, researchers have designed a recently launched clinical study into entrectinib, a first-inclass inhibitor of tropomyosin receptor kinases (Trk), as a basket trial in which the drug can be evaluated simultaneously for activity against three gene alterations and multiple tumor types.
“STARTRK-2 (NCT02568267) is an open-label, phase II study in which patients with locally advanced or metastatic solid tumors are assigned to different baskets according to whether their tumors harbor rearrangements in one of three key genes—NTRK1/2/3, ROS1, or ALK.”
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“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.”
“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.”
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“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 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.
“A rare and deadly form of skin cancer, known as desmoplastic melanoma (DM), has been found to contain more gene mutations than any other cancer so far.
“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.”