E-Book Overview
Leading clinical and laboratory scientists describe cutting-edge methods for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumors. The protocols contain detailed instructions and extensive troubleshooting tips that allow researchers effectively to study a wide variety of drug resistance mechanisms, including aspects of drug-induced cell death, drug uptake/efflux, drug metabolism, and DNA repair. Each method is designed to help identify the correlation between molecular and biochemical data and the clinical responses of the patient. Cytotoxic Drug Resistance Mechanisms illuminates all the clinically relevant mechanisms used as markers of the biological response to anticancer biotherapeutics today.
E-Book Content
Drug Resistance
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1 Drug Resistance The Clinical Perspective D. Alan Anthoney and Stanley B. Kaye 1. Introduction There are very few tumor types in which the use of chemotherapy can bring about prolonged survival, and possibly cure, for individual patients. The most common reason for this is the development of drug resistance within tumor cells. The laboratory study of resistance to anticancer drugs has resulted in the discovery of numerous mechanisms present within tumor cells that act to reduce their cytotoxic effects. However, the failure to translate this basic laboratory research into improved clinical outcome for patients remains one of the most pressing problems in contemporary cancer research. Clinical drug resistance encompasses two broad categories of treatment failure. Innate drug resistance is observed when a patient’s disease fails to respond to therapy initially. Acquired resistance arises with the development of tumor recurrence at some time after completion of initial treatment. The recurrent disease often displays resistance to anticancer agents to which it has had no prior exposure. Although cell