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Gene Study Sheds New Light on Lung Cancer

Posted by Chrissie Cole
Thursday, October 23, 2008 12:08 PM EST
Category: Major Medical
Tags: FDA and Prescription Drugs, Lung Cancer, Cancer, Rapamycin, Colon Cancer, DNA, Cigarette Smoking

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IMAGE SOURCE: © iStockPhoto / Lung Cancer slide / author: JamesBenet

A large new study by the National Institutes of Health more than doubles the number of genes associated with lung cancer and points to new treatment options.

Researchers examined DNA sequences from more than 600 genes in tumor samples taken from 188 patents with lung adenocarcinoma, the most common form of lung cancer.

Lung cancer claims the lives of more than one million people worldwide each year, including more than 150,000 people in the United States. The average 5-year survival rate is estimated at 15 percent, with survival being longest among those whose cancer is detected in the early stages.

The study, called the The Tumor Sequencing Project (TSP) found up to 26 genes that are frequently mutated in lung cancer tumors at high frequency. Earlier studies linked 10 gene mutations with lung cancer – and only five of them were known to be mutated at high frequency.

Nearly 90 percent of lung cancer patients have long standing histories of cigarette smoking, but 10 percent report no use of tobacco. Smokers’ tumors carried up to 49 mutations. While none of the tumors from non-smokers was found to have more than five mutations.

More research is needed to determine what these differences mean for the management of lung cancer. However, doctors do know that in some forms of cancer, high mutation levels may cause a tumor to rapidly spread and/or be resistant to treatment.

Two-thirds of the tumors were found to carry a mutation in a gene that affects a chemical pathway called mitogen-activated protein kinase (MAPK). Which suggests this group of compounds affects the MAPK pathway – the MEK inhibitors – and may be particularly effective.

More than two-thirds of the tumors carried a mutation in a gene affecting a chemical pathway called mitogen-activated protein kinase, also known as MAPK. This suggests that a group of compounds that affect the MAPK pathway – the MEK inhibitors – may be effective. The same compounds have shown promise in a mouse model of colon cancer.

The findings also raise hope for Rapamycin, an existing drug approved for use in kidney cancer and organ transplants that affects the mTOR chemical pathway. Approximately a third of the lung tumors examined in the gene study were found to affect the mTOR pathway.

“Our research paves the way for many new therapy targets for this deadly disease,” said Matthew Meyerson, MD, PhD, MIT and Harvard researcher.

The study was funded by the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) and published in the October 23 issue of the journal Nature. #


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