Drug Resistance and Its Clinical Circumvention

Abstract

Overview Tumors initially sensitive to chemotherapeutic agents frequently develop resistance to them, resulting in the familiar clinical pattern of initial response followed by a recurrence that no longer responds to therapy. Laboratory and clinical investigation have identified a plethora of drug resistance mechanisms, some that are particular to an individual agent and others that are applicable across classes of agents. These mechanisms include altered cellular accumulation and detoxification of drugs, mutation of the drug target, change in expression of the drug target, and activation of alternative signaling pathways. The identification of drug resistance mechanisms has led to strategies to overcome resistance and improved clinical outcomes.