Emerging approaches to target mitochondrial apoptosis in cancer cells

Apoptosis is a highly conserved programme for removing damaged and unwanted cells. Apoptosis in most cells is coordinated on mitochondria by the Bcl-2 family of proteins. The balance between pro- and anti-apoptotic Bcl-2 family proteins sets a threshold for mitochondrial apoptosis, a balance that is altered during cancer progression. Consequently, avoidance of cell death is an established cancer hallmark. Although there is a general perception that tumour cells are more resistant to apoptosis than their normal counterparts, the realities of cell death regulation in cancer are more nuanced. In this review we discuss how a profound understanding of this control has led to new therapeutic approaches, including the new class of BH3-mimetics, which directly target apoptosis as a vulnerability in cancer. We discuss recent findings that highlight the current limitations in our understanding of apoptosis and how these novel therapeutics work.