Therapy-induced apoptosis in primary tumors.

An enormous body of literature has accumulated over the past 15 years implicating apoptosis (programmed cell death) in breast cancer cell death induced by conventional and investigational cancer therapies in preclinical models. As a result, new therapeutic approaches that directly target key components of apoptotic pathways are either entering or will soon enter clinical trials in patients, raising hopes that the information gained from the preclinical studies can be translated to improve patient care. However, there is a new appreciation for the fact that apoptosis is not the only relevant pathway that mediates physiological cell death, and many investigators are challenging the notion that targeting apoptosis is the best means of optimizing therapeutic efficacy in primary tumors. Here I will review some of the basic concepts that have emerged from the study of apoptosis in preclinical models, the evidence that apoptosis does or does not mediate the effects of current front line therapies in patients, and the new strategies that are emerging that are designed to more directly target apoptotic pathways.