Evolution of Anticancer Drug Discovery and the Role of Cell-Based Screening

Abstract

The approach to the discovery of new anticancer drugs has recently evolved from a reliance on empiric cell-based screening for antiproliferative effects to a more mechanistically based approach that targets the specific molecular lesions thought to be responsible for the development and maintenance of the malignant phenotype in various forms of cancer. The ultimate goal of the development of molecularly targeted drugs is to improve the efficacy and selectivity of cancer treatment by exploiting the differences between cancer cells and normal cells. The success of recently developed molecularly targeted agents, such as tretinoin (all-trans-retinoic acid) for acute promyelocytic leukemia (1,2) and imatinib (STI-571) for chronic myelogenous leukemia (CML) (3,4) and gastrointestinal stromal tumors (5), provides early clinical validation for the molecularly targeted approach to drug discovery.