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IU investigators find biomarker that predicts taxane-induced neuropathy among breast cancer patients

INDIANAPOLIS -- (May 24, 2011) -- Indiana University researchers have identified a genetic biomarker that causes neuropathy among some breast cancer patients using a class of chemotherapy drugs called taxanes.

It is one of the first genetic biomarkers to have been reported for neuropathy caused by taxanes, which includes paclitaxel or Taxol. The finding may eventually lead to a blood test to determine if a patient is at risk of developing neuropathy. 

Neuropathy is a nerve problem that causes pain, numbness, tingling, burning, or muscle weakness in different parts of the body. 

“We found multiple, provocative genes that may be associated with neuropathy, one of which stood out from the rest in a gene named RWDD3,” Bryan Schneider, M.D., the lead investigator, said. Dr. Schneider is assistant professor of medicine, assistant professor of medical and molecular genetics at the IU School of Medicine, and a physician/researcher at the Indiana University Melvin and Bren Simon Cancer Center. He is also an associate director of the Indiana Institute for Personalized Medicine

Dr. Schneider and colleagues found the gene by conducting a comprehensive genetic look of more than one million genetic variations in each of the 2,204 breast cancer patients studied. The patients were enrolled in the Eastern Cooperative Oncology Group clinical trial E5103.

The IU investigators looked for variations in DNA called single nucleotide polymorphisms or SNPs. They identified genetic subgroups that were likely to develop neuropathy. Those who carried two normal nucleotides in the RWDD3 gene had a 27 percent chance of experiencing neuropathy. But those who carried one normal nucleotide and one SNP had a 40 percent chance and those who carried two SNPs had a 60 percent chance.

The study also found that older patients and African Americans were much more likely to have neuropathy.

Dr. Schneider and colleagues will advance their research with additional trials to validate these findings and to determine whether a different type of taxane therapy would result in less neuropathy in the more susceptible genetic group.

Dr. Schneider’s research caught the attention of the world’s leading professional organization representing physicians who care for people with cancer, the American Society of Clinical Oncology.  ASCO has invited Dr. Schneider to present his research findings during its 47th annual meeting in Chicago in early June. His research also has been selected to be highlighted in ASCO’s official press program.  Less than 1 percent of abstracts are chosen for that distinction. The press program plays a vital role in garnering accurate, national media coverage of cancer research presented at the meeting. In addition, Dr. Schneider’s research has been selected to be included in the Best of ASCO program, an educational initiative that seeks to increase global access to cutting-edge science.

Dr. Schneider’s IU collaborators were: Sunil Badve, M.D.; David Flockhart, M.D., Ph.D.; Tatiana Foroud, Ph.D.; Brad Hancock, B.S.; Nawal Kassem, M.S.; Daniel Koller, Ph.D.; Lang Li, Ph.D.; Zhuokai Li, Ph.D.; Kathy Miller, M.D.; Milan Radovich, Ph.D.; and George Sledge, M.D. Other collaborators were Chua Dang, M.D., of Memorial Sloan-Kettering; Anne O'Neill of Dana-Farber Cancer Institute; Donald Northfelt, M.D., of Mayo Clinic; Ann Partridge, M.D., M.P.H., of Dana-Farber Cancer Institute; Elda Railey and Mary Lou Smith of Research Advocacy Network; and Joseph Sparano, M.D., of Albert Einstein College of Medicine.