Patients With Susceptibility Gene Are Poor Candidates For Some Chemotherapies.

2001 APR 19 - (NewsRx.com & NewsRx.net) -- Researchers have found that alterations in a breast cancer susceptibility gene can change the effectiveness of certain chemotherapy drugs against the disease.

The work highlights the new field of pharmacogenomic therapy, which has become increasingly important with the sequencing of the human genome and, it is hoped, will lead to improved cancer therapies.

The findings, reported March 27, 2001, at the annual meeting of the American Association for Cancer Research, may warrant oncologists to reconsider using certain chemotherapy agents for those women with breast cancer who carry the altered gene, known as BRCA1.

The scientists, led by Bruce Turner, MD, PhD, assistant professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania, and at Jefferson's Kimmel Cancer Center and John C. Reed, MD, PhD, scientific director of the Burnham Institute in La Jolla, California, found that breast cancer cells with mutations in BRCA1 are sensitive to certain chemotherapy drugs and radiation, but resistant to others, such as the widely used anti-breast cancer drugs taxol and taxotere. These drugs are frequently used in combinations with other chemotherapy agents in young women with breast cancer or in those with advanced disease.

When the researchers looked at breast tumors in women with BRCA1 mutations, they found cancer cells lacking the Bcl-2 gene protein, which appears important for the effectiveness of taxol and which also inhibits apoptosis, or programmed cell death.

Turner and his co-workers found that normal BRCA1 regulates Bcl-2 gene expression on a molecular level and this regulation may be important in prodding breast cancer cells into ...