Charles S. Morrow

The emergence of anticancer drug resistance constitutes a major problem in the successful treatment of advanced or disseminated cancers with conventional cancer drugs. Hence, a major focus of our research has been to understand the roles in the emergence of cancer drug resistance of the drug metabolizing enzymes and the membrane-associated transporters that remove drugs and their metabolites from cells. In particular, we have been interested in how combined expression of glutathione transferases (GST)––drug conjugating enzymes––and multidrug resistance proteins (MRP)––a family of drug and drug conjugate efflux transporters––influence drug resistance in cancer cells. Additionally, as the chemical properties of cancer drugs, carcinogens, and other cellular toxins frequently overlap, we have also investigated how the interplay between GST and MRP affects the sensitivity of cells to carcinogen exposure. Indeed our laboratory has shown that, for many cancer drugs, carcinogens, and other toxins, GST and MRP can act cooperatively, and often in synergy, to confer drug resistance in cancer cells and carcinogen resistance in normal cells.

More recently, we have shown that MRP and GST can modulate the activities of some potent and chemically reactive lipid signaling molecules including the oxo- and nitro-derivatives of endogenous unsaturated fatty acids.

Inspired by these and other studies, additional areas of ongoing research include a clinical study to determine the prognostic significance of MRP and GST expression in chronic leukemia and a preclinical study to evaluate novel approaches to the treatment of breast cancer using conventional chemotherapeutic drugs in combination with lipid and pharmaceutical signaling molecules.

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