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Susan Bates, M.D.
Reversal of Drug Resistance: Clinical and Laboratory Approaches
Achieving a clinical response to chemotherapy has proven to be simple in some diseases, and almost impossible in others. Our laboratory focus has been on understanding drug resistance, which can be broadly defined as the simultaneous resistance to a variety of chemically unrelated chemotherapeutic agents. This multidrug resistance is present at the time of diagnosis in some tumor types, such as in renal cell carcinoma, or occurs following one or more courses of chemotherapy in more responsive diseases, such as breast cancer. Our goal is to identify combination therapies that overcome drug resistance, or to identify antineoplastic agents that circumvent resistance. Our laboratory studies have led to insights in cancer biology related to drug efflux pumps. Our group has studied ABCG2, a multidrug transporter able to confer resistance to a variety of chemotherapeutics. ABCG2 is interesting for its role in the blood brain barrier and in normal tissue protection.
Our group has been involved in the clinical and translational development of romidepsin, a histone deacetylase (HDAC) inhibitor, leading to our current area of focus on epigenetic therapies, and on the development of combination therapies to use with HDAC inhibitors. We have intensively studied the mechanism of action of HDAC inhibitors such as romidepsin (formerly depsipeptide), examining effects in both T-cell lymphoma and in solid tumor cells. We have established non-Pgp-expressing romidepsin-resistant cell lines in the laboratory with the goal of understanding mechanisms of resistance and then identifying other agents to be used in combination to overcome these resistance mechanisms. For example, overexpression of phospho-MEK in romidepsin-resistant cells appears to be a mechanism of resistance, and the addition of MEK inhibitors to romidepsin is an approach that we can take to improve outcome. Our goal is to translate this and other ideas to clinical trial.
This page was last updated on 6/28/2014.