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April 2013 Issue

Lung Cancer Study Shows Potential for More Targeted Therapies 

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Histological tissue section from a sample of lung squamous carcinoma. Image courtesy of the National Cancer Institute.

In 2008, scientists at The Genome Institute at Washington University became the first in the world to sequence the genome of a cancer patient. By sequencing donated cells of a
patient who died of leukemia, scientists were able to compare her own genome with the genome of her tumor cells to identify the
genetic errors that likely caused her cancer. The success of this endeavor has led to other landmark projects that have allowed for the sequencing of hundreds of cancer patients' genomes.

Many studies, including the recent squamous
cell lung cancer study, are now based on genome sequencing, which involves spelling out the precise order of the three billion chemical letters that make up a molecule of DNA. While the order of those letters varies slightly from person to person, the challenge for scientists has been to determine which variations are considered "healthy" and which can contribute to cancer or other genetic diseases.

The Cancer Genome Atlas Project combines efforts of the nation's leading genetic sequencing centers, including The Genome Institute, to describe the genetics of common tumors. The goal is to improve prevention, detection and treatment.

Explaining the importance of the squamous cell lung cancer study, Ramaswamy Govindan, MD, a medical oncologist specializing in lung cancer at the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine and co-chair of the lung cancer group of The Cancer Genome Atlas, says, "For the first time, instead of looking through a keyhole, we are getting a penthouse panoramic view of this disease's genetic makeup. Rather than focusing on a handful of genes, as has been done in the past, this study has revealed complex changes across the entire genome."

The study is the first comprehensive genetic analysis of squamous cell carcinoma of the lung. This common type of lung cancer is 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 available commercially or that are in development," says Govindan.

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Ramaswamy Govindan, MD.

The study examined both the tumor cells and normal tissue of 178 patients with lung squamous cell carcinoma. The investigators found recurring mutations common to many patients in 18 of the 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. This discovery further supports the emerging body of evidence that cancers may be more appropriately classified by genetics rather than the primary organs they affect.

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.

"With this analysis, we are just starting to understand the molecular biology of lung squamous cell carcinoma," says Govindan. "And now we have identified potential targets for therapies to study in future clinical trials." He adds, "This 'cataloging' approach will help us transform cancer clinical trials by separating patients according to their mutations and providing treatment accordingly."

In the future, this could mean a certain type of lung cancer would be treated with a drug approved as a treatment for breast cancer if both carried similar genetic mutations. This type of targeted therapy, based on the genetics of cancer cells, has the potential to determine the most effective treatments for patients.