New frontiers in promoting tumour cell death: targeting apoptosis, necroptosis and autophagy

Cancer is a multifaceted disease comprising a combination of genetic, metabolic and signalling aberrations, which severely disrupt the normal homeostasis of cell growth and death. Many oncogenic events while promoting tumour development also increase the sensitivity of cells to cell death stimuli including chemotherapeutic drugs. As a result, tumour cells often acquire the ability to evade death by inactivating cell death pathways that normally function to eliminate damaged and harmful cells. The impairment of cell death function is also often the reason for the development of chemotherapeutic resistance encountered during treatment. It is therefore necessary to achieve a comprehensive understanding of existing cell death pathways and the relevant regulatory components involved, with the intention of identifying new strategies to kill cancer cells. This review provides an insightful overview of the common forms of cell death signalling pathways, the interactions between these pathways and the ways in which these pathways are deregulated in cancer. We also discuss the emerging therapies targeted at activating or restoring cell death pathways to induce tumour cell death, which are currently being tested in clinical trials. Oncogene (2012) 31, 5045-5060; doi: 10.1038/onc.2012.7; published online 6 February 2012