Large lung cancer study shows potential for more targeted therapies

A nationwide consortium of scientists has reported the first comprehensive genetic analysis of squamous cell carcinoma of the lung, a common type of lung cancer responsible for about 400,000 deaths each year.

"We found that almost 75 percent of the patients' cancers have mutations that can be targeted with existing drugs - drugs that are available commercially or for clinical trials," says one of the lead investigators, Ramaswamy Govindan, MD, an oncologist at Washington University School of Medicine in St. Louis and co-chair of the lung cancer group of The Cancer Genome Atlas.

The Cancer Genome Atlas project combines efforts of the nation's leading genetic sequencing centers, including The Genome Institute at Washington University, to describe the genetics of common tumors with the goal of improving prevention, detection and treatment. The Cancer Genome Atlas is supported by the National Cancer Institute and the National Human Genome Research Institute, both parts of the National Institutes of Health (NIH).

The other lung cancer co-chairs are the study's senior author Matthew Meyerson, MD, PhD, of the Broad Institute of Massachusetts Institute of Technology and Harvard University, and Stephen Baylin, MD, of Johns Hopkins University.

The study examined the tumors and normal tissue of 178 patients with lung squamous cell carcinoma. The investigators found recurring mutations common to many patients in 18 genes. And almost all of the tumors showed mutations in a gene called TP53, known for its role in repairing damaged DNA.

Interestingly, the researchers noted that lung squamous cell carcinoma shares many mutations with head and neck squamous cell carcinomas, supporting the emerging body of evidence that cancers may be more appropriately classified by their genetics rather than the primary organ they affect.

"We clearly see mutations in lung cancer that we see in other human cancers," says Richard K. Wilson, PhD, director of The Genome Institute at Washington University. "This reinforces something that we've been seeing in a lot of our cancer genomics work. It's really less about what type of tissue the tumor arises in - lung, breast, skin, prostate - and more about what genes and pathways are affected."

Current treatment for squamous cell lung cancers includes chemotherapy and radiation, but there are no drugs specifically designed to target this particular type of lung cancer. Squamous cell lung cancer is linked to smoking and responsible for 30 percent of all lung cancer cases.

"With this analysis, we are just starting to understand the molecular biology of lung squamous cell carcinoma," says Govindan, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University. "And now we have identified potential targets for therapies to study in future clinical trials."

The Cancer Genome Atlas Research Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. Sept. 9, 2012

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

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