Introduction

Apoptosis, or programmed cell death, is an evolutionary conserved genetic process of cellular suicide, which plays a crucial role in sculpting the developing organism and in “pruning” billions of unwanted, unneeded, or damaged cells every day during adult life (1). Aberrations of apoptosis leading to abnormal cell viability or excess cell death contribute to the pathogenesis of human diseases (2). However, these alterations are particularly important in cancer, where they impact virtually every facet of the disease, from onset to progression to treatment (3). As our knowledge of apoptotic pathways has dramatically increased over the past decade, so have the opportunities to harness this powerful cellular suicidal program for novel molecular cancer therapeutics (4).

As a result, apoptosis-based therapy is now a reality, and several new agents engineered to (re)awaken various mechanisms of cell death in tumors have entered clinical testing (5), producing, at least in some cases, intriguing, if not spectacular, patient responses. The early clinical trials have also opened fresh prospects for further elucidation of basic cell-death mechanisms, and identified key molecular requirements for sensitivity or resistance to this new class of therapeutics. From a drug-development perspective, the design of apoptosis-targeting agents has often defied conventional tenets of what may constitute a “drugable” target, and unlocked avenues for innovative drug-discovery platforms.