The role of protein kinase C in multidrug resistance

Abstract

The development of resistance to anticancer agents during treatment is a major obstacle to successful cancer therapy [1–3]. In addition, certain tumor cells exhibit de novo resistance to anticancer agents. De novo resistance is commonly observed in renal, gastric, and colon cancers, and it precludes successful treatment of these diseases with chemotherapeutic drugs [2]. Cultured tumor cell populations often acquire a multidrug resistance (MDR) phenotype after prolonged exposure to cytotoxic natural products such as anthracyclines, vinca alkaloids, and epipodophyllotoxins [1–3]. MDR tumor cells are by definition resistant to the cytotoxic effects of the selecting agent and cross-resistant to cytotoxic natural products that are structurally diverse but generally have in common the ability to produce MDR tumor cells from drug-sensitive tumor cell populations [1-3]. Patterns of cross-resistance observed among different MDR tumor cell lines are variable and unpredictable. Because many of the cytotoxic natural products linked to the MDR phenotype are anticancer agents [1–3], it is believed that an understanding of the MDR phenotype could potentially lead to significant improvements in cancer theraphy [1].