Dr. Couch aims to develop a better understanding of the genetic events that cause resistance to taxol and platinum drugs, the standard chemotherapy combination treatment for ovarian cancer. The goal is to identify as many genes as possible that contribute to drug resistance. Other groups have studied resistance by identifying genes that are turned on or off in response to the chemotherapeutic drugs. However, few have tried to identify genes that normally play a role in the development and progression of tumors and which may also influence the response to the drugs. Dr. Couch has searched for these development and progression genes by studying a specific set of tumors that were collected during surgery, before the patients received therapy. By following these patients over time after they received their chemotherapy, he has identified tumors that recurred rapidly or were resistant to taxol and platinum therapy and those that did not recur for a long period and were sensitive to taxol and platinum therapy. It seems likely that many of these tumors were intrinsically resistant or sensitive to these agents. Such tumors form a unique resource for identifying the genes involved in progression and resistance. Dr. Couch has evidence to suggest that several of these genes are actually oncogenes, or cancer causing genes, that are amplified in copy number and cause the tumors to grow more rapidly. In the study, he will search for all sites of amplification in the tumors collected and will identify amplified genes that are statistically associated with resistance or sensitivity to platinum and taxol. Findings should lead to a better understanding of genes implicated in drug resistance and sensitivity.
Dr. Fergus Couch is a Professor of Laboratory Medicine and Pathology at the Mayo Clinic in Rochester, MN.