Mutations within a small cluster of genes tied to tumor growth are involved in three-quarters of the cases of the most common form of lung cancer, according to a study that could help link treatment to specific genetic flaws.
The research is the most comprehensive genomic analysis of adenocarcinoma, a cancer that forms in the tissues near the outer parts of the lungs and is usually linked to smoking, though it can occur in nonsmokers. Researchers identified 18 key mutations in an examination of 230 adenocarcinoma lung tumors, according to the study published today in the journal Nature.
The finding adds to the range of genetic alterations known to be involved in lung cancer. In addition to leading to new drugs against new tumor targets, it may also help identify more patients who can be treated with cancer medicines already on the market that target specific growth-promoting proteins.
“To treat lung cancer you are not going to have a silver bullet, you are going to need a lot of different combinations of treatments against different targets,” said Matthew Meyerson, a professor of pathology at Harvard Medical School and a lead investigator on the study.
In particular, more than three-quarters of patients had changes in a cluster of related genes called the RTK/RAS/RAF pathway. Mutations in this group of genes can cause growth signals to become stuck in the on position, promoting runaway tumor expansion.
While the signaling pathway has long been known to be involved in lung cancer, the study found additional types of mutations in the pathway. Some patients have mutations in a gene called RIT1 that was not known to be altered in lung cancer, according to the research.
The study also confirmed and solidified previous findings that some lung tumors have abnormalities in a gene called MET, said Meyerson, who is also at the Broad Institute in Cambridge and the Dana-Farber Cancer Institute. That suggests that Xalkori from Pfizer Inc. (PFE:US), a drug already approved for treating lung cancer patients with an abnormality in a gene called ALK, might also help in patients with MET alterations, Meyerson said.
The lung cancer data are part of a broader project by the National Institutes of Health called the Cancer Genome Atlas, which is analyzing samples from numerous types of malignancies. In 2012, the project’s researchers had examined another less common type of lung cancer, squamous cell, and found mutations in 11 genes from 178 tumors they sequenced.
Other Cancer Genome Atlas studies have analyzed mutations in ovarian cancer, colon cancer, acute myeloid leukemia, and breast cancer.
Roughly 224,000 new cases of lung cancer will be diagnosed in the U.S. this year, and 159,000 Americans will die from the disease, according to data from the American Cancer Society.
Meyerson is a founding adviser to Foundation Medicine Inc., (FMI:US) a Cambridge, Massachusetts company that sells a test to spot genetic abnormalities in tumors.
“This is the most comprehensive genomic analysis done” in adenocarcinoma, he said. “It will be a really useful resource for those who are working in this area.”
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