Drug Resistance & Metabolism

Chemotherapy of many types of cancer fails to achieve a cure either because the tumors are inherently resistant to a wide range of cytotoxic drugs and differentiating agents, or they acquire such characteristics following an initial response. We are involved in the identification, cloning and characterization of proteins responsible for these resistance mechanisms. Studies to date have resulted in discovery of: the Multidrug Resistance Protein (MRP) which is capable of conferring resistance to a wide range of commonly used natural product chemotherapeutic agents; topoisomerase II mutations that reduce its nuclear localization causing resistance to drugs targeting this enzyme; a candidate protein that may be involved in development of resistance to platinum based drugs; CYP26 which is a novel retinoid inducible cytochrome P450 that may catalyze the rate limiting step in retinoid catabolism, and a mechanism by which xenobiotics can induce changes in expression of the major serum high density apolipoprotein, ApoAI, that may enhance hepatic elimination of these compounds. More detailed information can be obtained from the personal pages of individual investigators.

Susan P.C. Cole
Mechanisms of Resistance to Anticancer Drugs and Transport of Chemical Toxicants 

Roger G. Deeley
Gene Expression/Drug Resistance 

P. Martin Petkovich
Retinoic Acid Receptors in Development and Differentiation