Getting back on track, or what to do when apoptosis is de-railed: Recoupling oncogenes to the apoptotic machinery

Abstract

Programmed cell death or apoptosis is of fundamental importance to cancer as it both limits tumorigenesis and is also triggered by many cancer chemotherapeutics. Many oncogenes that deregulate the cell cycle also trigger apoptosis, so eliminating cells that are proliferating inappropriately. To acquire a complete neoplastic phenotype, cancer cells often acquire mutations that compromise the apoptotic process, allowing these cells to escape both normal growth constraints but to also become resistant to many anti-cancer drugs and leading to the emergence of drug-resistant malignancies. Thus discovering how oncogenes are coupled to apoptosis and how these links are compromised in cancer is central to both understanding cancer progression and developing new therapies to counter chemo-resistant cancers. This review will consider how oncogenes activate apoptosis and how this response is subverted in cancer cells with a focus on the proposed therapeutic strategies that exploit these changes. ©2004 Landes Bioscience.