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TGen and Genomic Health Inc. discover genes affecting cancer drug

Laboratory study indicates need for more clinical research of mechanisms that influence the activity of oxaliplatin

Genomic research could help doctors better target a drug widely used to treat colorectal cancer patients, according to a study by Genomic Health Inc. (Nasdaq: GHDX) and the Translational Genomics Research Institute (TGen).

The drug, oxaliplatin, is widely used in colon cancer. It is used in early disease, following surgery in those cancers that are likely to recur. It is also used in advanced disease to slow progression of the cancer where it has spread to other parts of the body.

However, a significant number of patients experience serious side effects, including prolonged damage to the nervous system, "creating an urgent need to identify genes that are responsible for drug sensitivity or resistance, which results in directing therapy to those most likely to benefit," according to the study published in Molecular Cancer Research.

Colorectal cancer is the third most common type of cancer in the U.S., annually diagnosed in more than 146,000 Americans. It also is the third highest cause of cancer death in the U.S., annually killing nearly 50,000 people, more than who die each year on the nation's roadways. This cancer affects men and women in nearly equal numbers.

Nerve damage, or neurotoxicity, associated with oxaliplatin is most commonly manifest as pain or a loss of sensation in the hands and feet and can severely affect a patient's quality of life and ability to work. These symptoms are experienced in some form by the majority of patients receiving this drug and, for some patients, can be permanent.

The TGen/Genomic Health researchers examined the role of individual cancer genes to influence the sensitivity or resistance of colon cancer cells grown in laboratory culture. An interfering RNA screen of 500 genes — with 2,000 unique siRNA sequences —identified 27 genes that, when silenced, altered the sensitivity of colon tumor cells to oxaliplatin, causing damage to the cancer cells' DNA and inhibiting the cancer cells' ability to reproduce and survive, the study said. This study has also showed that diverse gene networks also play a role in the ability of the drug to impact colon tumors.

"These 27 genes, whose loss of function significantly affect the effectiveness of oxaliplatin, may be promising therapeutic biomarkers for oxaliplatin," said Dr. Holly Yin, head of TGen's Cellular Genomics Collaborative Center in Scottsdale, and a co-author of the study.

Dr. Robert J. Pelham, a research scientist at Redwood City, Calif.-based Genomic Health and the study's senior author, said the findings indicate a need for additional clinical studies on tumor specimens in patients treated with oxaliplatin. "Such future clinical studies could eventually lead to potential clinical applications, where patients could benefit," Dr. Pelham said.

This laboratory study has been published online and is pending print publication in Molecular Cancer Research, one of six peer-reviewed scientific journals published by the Philadelphia-based American Association for Cancer Research. Founded in 1907, AACR is the world's oldest and largest scientific organization focused on high-quality, innovative cancer research.

About Genomic Health Inc.

Genomic Health, Inc. (NASDAQ: GHDX) is a molecular diagnostics company focused on the global development and commercialization of genomic-based clinical laboratory services that analyze the underlying biology of cancer allowing physicians and patients to make individualized treatment decisions. Its lead product, the Oncotype DX® breast cancer test, has been shown to predict the likelihood of chemotherapy benefit as well as recurrence in early-stage breast cancer. In addition to this widely adopted test, Genomic Health provides the Oncotype DX colon cancer test, the first multigene expression test developed for the assessment of risk of recurrence in patients with stage II disease. As of September 30, 2010, more than 10,000 physicians in over 55 countries had ordered more than 175,000 Oncotype DX tests. Genomic Health has a robust pipeline focused on developing tests to optimize the treatment of prostate and renal cell cancers, as well as additional stages of breast and colon cancers. The company is based in Redwood City, California with European headquarters in Geneva, Switzerland. For more information, please visit

Press Contact:
About TGen
The Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. TGen is affiliated with the Van Andel Research Institute in Grand Rapids, Michigan. For more information, visit:
Press Contact:
Steve Yozwiak
TGen Senior Science Writer

Steve Yozwiak | EurekAlert!
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