CLINICAL-EVALUATION OF BIOLOGICALLY TARGETED DRUGS - OBSTACLES AND OPPORTUNITIES

Recent insights into the molecular mechanisms of cancer have indicated that a variety of fundamental cellular processes are dysregulated in malignant cells. These processes include cell cycle control, signal tr ansduction pathways, apoptosis, telomere stability, angiogenesis, and interactions with the extracellular matrix. Remarkable advances in mol ecular genetics, enzymology, and medicinal chemistry have permitted th e design of compounds that modulate some of these processes with speci ficity that was unimaginable a decade ago. As these novel, biologicall y targeted compounds enter the clinic, they will require a strategy fo r clinical evaluation and development different from that used commonl y for cytotoxic antineoplastic agents. This review examines the develo pment of cancer drugs directed against angiogenesis, metastasis, signa l transduction, telomerase, and molecular message (antisense), outline s strategies for the clinical testing of agents directed at these proc esses, and contrasts these efforts with traditional approaches to canc er drug testing.