For Immediate Release:
Feb. 13, 2012 <\/p>\n
Newswise \u2014 BOSTON\u2014Novel gene abnormalities discovered in a subpopulation of lung and colorectal tumors could potentially identify patients with a good chance of responding to highly specific \u201ctargeted\u201d drugs already in use for treating other cancers, scientists report. <\/p>\n
The genetic alterations \u2013 pieces of two genes fused together - showed up in a massive search of the DNA in stored tumor samples of non-small cell lung cancer and colorectal cancer, said researchers from Dana-Farber Cancer Institute and Foundation Medicine, Inc. These specific genetic abnormalities had not been previously linked to the two cancer types. <\/p>\n
Their results were published online by the journal Nature Medicine.
Other cancers with similar genetic alterations often respond to \u201ctargeted\u201d drugs s that block overactive proteins called tyrosine kinase inhibitors. This suggests that the same drugs also may be effective against lung and colorectal tumors driven by the newly found gene fusions. Because these drugs are already approved to treat cancer, it should be possible to move rapidly to clinical trials in colorectal and lung cancer, the authors said. <\/p>\n
If the trials are successful, physicians could potentially test patients' tumors for the presence of the gene fusions and prescribe a medication matched to those alterations, said Pasi A. J\u00e4nne, MD, PhD, a thoracic oncologist at Dana-Farber and co-senior author of the report along with Philip J. Stephens, PhD, and Maureen Cronin, PhD, of Foundation Medicine. Doron Lipson, PhD, is the paper\u2019s first author.
\u201cThis is a textbook example of personalized medicine for lung cancer \u2013 a genetic alteration found in a subset of patients that we can now look for and use as a means to select particular therapies,\u201d J\u00e4nne said. <\/p>\n
\u201cIn the past, although these targeted drugs were available, they were not chosen for a particular subset, but instead given to everybody,\u201d he explained. \u201cThis will increase the likelihood of those therapies being more successful.\u201d <\/p>\n
The researchers estimate that less than 1 percent of Caucasians and about 2 percent of Asians with lung cancers carry this alteration \u2013 a fusion gene labeled KIF5B-RET. However, they said the finding opens a significant therapeutic opportunity. <\/p>\n
\u201cIn a common indication like non-small cell lung cancer, identifying even a small subpopulation of individuals with gene fusions who may be responsive to a targeted therapy has the potential for major therapeutic impact,\u201d said Stephens, executive director of cancer genomics at Foundation Medicine. \u201cThis joint research with Dana-Farber translates genomic research to the clinic and we expect that it may quickly have a positive impact for patients.\u201d <\/p>\n
The American Cancer Society projects that 226,160 Americans will be diagnosed with lung cancer in 2012 and 160,340 will die of the disease. <\/p>\n
Foundation Medicine scientists identified the novel fusion gene in a DNA tumor sample removed from a 44-year-old man with non-small cell lung cancer (NSCLC) who had never smoked. The hybrid gene is composed of a piece of a cell growth gene, RET, and part of another gene, KIF5B. This abnormal gene combination causes RET to act like a growth switch stuck in the \u201con\u201d position, spurring uncontrolled cell division. <\/p>\n
The company formed a collaboration with J\u00e4nne and his Dana-Farber colleagues to follow up the discovery. \u201cWe looked for the RET fusion gene in a larger collection of lung tumor samples to determine how common it is, and if it is acting as an oncogene [a gene that drives cancer]\u201d said J\u00e4nne. They searched samples from 121 Caucasian patients and 405 Asian patients who had never smoked or had rarely smoked in the past.
The RET fusion gene was detected in 1 of the Caucasian samples (0.8 percent) and 9 of the Asian patient samples (2 percent). <\/p>\n
Thyroid cancers containing RET gene hybrids are known to respond to certain targeted drugs that inhibit RET. When Dana-Farber investigators tested three such inhibitors \u2013 sorafenib, sunitinib and vandetinib \u2013 on cultured cells containing the newly discovered RET mutation, each of the drugs killed those cells, the scientists reported.
J\u00e4nne noted that some patients with NSCLC have responded to treatment with these inhibitor drugs. The researchers want to find out whether those patients had RET mutations in their tumors. <\/p>\n
The Foundation Medicine scientists also sequenced DNA samples from 40 patients with colorectal cancer. Along with numerous known mutations, the researchers identified a novel gene alteration, C2orf44-ALK, that causes a 90-fold overexpression of the ALK protein leading to cancerous proliferation. Overexpressed ALK is also found in a small percentage of lung cancer cases and can be inhibited by the targeted drug crizotinib. This raises the possibility of using crizotinib to target the C2orf44-ALK fusion gene in colorectal cancer, the researchers said. <\/p>\n
In addition to Cronin, J\u00e4nne, Lipson and Stephens, the paper\u2019s co-authors were from Sharett Institute of Oncology, Jerusalem; TEVA Pharmaceutical Industries, Petach Tikva, Israel; Samsung Medical Center, Seoul, Korea; Nagoya City University Graduate School of Medical Sciences, Japan; Asan Medical Center, Seoul, Korea; and Albany Medical Center, New York. <\/p>\n
The research was funded in part by the Dana-Farber\/Harvard Cancer Center Lung Cancer SPORE grant from the National Cancer Institute and the Cammarata Family Foundation Research Fund. <\/p>\n
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber\/Harvard Cancer Center (DF\/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women\u2019s Hospital as Dana-Farber\/Brigham and Women\u2019s Cancer Center and it provides pediatric care with Children\u2019s Hospital Boston as Dana-Farber\/Children\u2019s Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter: @danafarber or Facebook: facebook.com\/danafarbercancerinstitute. <\/p>\n
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\nNewly Identified Fusion Genes in Lung and Colorectal Cancer May Guide Treatment with "Targeted" Drugs<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"