(Corrects 13th paragraph to clarify that Avastin is not a
By Julie Steenhuysen
CHICAGO Oct 22 A broad analysis of genes has
turned up 26 mutations linked with the most common form of lung
cancer, several of which play a role in other cancers as well,
researchers said on Wednesday.
The findings, published in the journal Nature, double the
number of genes already linked with lung adenocarcinoma, a type
of non-small cell lung cancer that accounts for 40 percent of
the more than 1 million lung cancer deaths each year.
"We think that our study may achieve a real impact on the
cure of lung cancer patients," Dr. Matthew Meyerson of the
Broad Institute of Massachusetts Institute of Technology and
Harvard University said in a telephone briefing.
Meyerson was part of an international team that decoded 623
genes from tumors in 188 lung cancer patients and compared
these to genes from normal tissues from the same people.
They found 26 genes that were most commonly altered in the
tumors, most of which had never been linked with lung cancer.
Some had been found in other types of tumors.
The new genes included mutations in neurofibromatosis 1, a
gene known to cause a rare neurological disorder and raise the
risk of nerve and brain tumors; ataxia telengiectasia mutated
or ATM, which has ties with leukemia and lymphoma;
retinoblastoma 1, which is linked with a rare childhood cancer
of the eye; and adenomatosis polyposis coli or APC, which is
common in colon cancer.
Many of the mutated genes also share common biological
pathways or gene networks.
"Looking at the pathways helps simplify the picture," said
Richard Wilson of Washington University in St. Louis, who
helped lead the project.
One of the most promising of these pathways is the
mitogen-activated protein kinase or MAPK pathway, altered in
more than 70 percent of the tumors. Drug compounds called MEK
inhibitors that affect this pathway have already shown promise
in mice with lung cancer.
About half of the tumors had defects in the p53 pathway,
which is critical for suppressing tumor growth. Companies such
as Introgen Therapeutics Inc (INGN.O) are working on drugs that
affect this pathway.
Some 30 percent of the tumors had mutations in the mTOR
pathway, raising hope that drugs that inhibit the mTOR protein
might help some lung cancer patients. Swiss drugmaker Novartis'
NOVN.VX mTOR inhibitor for kidney cancer, Afinitor, is
currently under review by U.S. regulators.
The researchers also saw that a familiar class of genes
known as tyrosine kinases, which trigger cell growth, played a
key role in lung tumors. Gene families in this group include
EGFR and VEGF.
Genentech DNA.N and Roche Holding AG's ROG.VX drug
Avastin targets VEGF, while their pill for advanced lung cancer
called Tarceva interferes with EGFR. A recent study found
combining the two did little to help lung cancer patients live
Meyerson said genetic testing may help determine which
patients might benefit from current drugs, but he said many new
drugs will likely come from the findings as well.
"Probably, we will need a lot more drugs. What's great is
we've identified many new drug targets," he said.
Some analysts predict the market for non-small cell lung
cancer could exceed $4 billion between 2010 and 2015.
(Editing by Maggie Fox and Cynthia Osterman)