How apoptosis is regulated, and what goes wrong in cancer

Programmed cell death (apoptosis) is an evolutionarily conserved pathway needed for embryonic development and tissue homoeostasis.1 Apoptosis is the normal physiological response to many stimuli, including irreparable DNA damage. Various diseases evolve because of hyperactivation (neurodegenerative diseases, immunodeficiency, ischaemia-reperfusion injury) or suppression of programmed cell death (cancer, autoimmune disorders).2

In cancer, the balance between proliferation and programmed cell death is disturbed, and defects in apoptotic pathways allow cells with genetic abnormalities to survive. Most cytotoxic and hormonal treatments, as well as radiation, ultimately kill cancer cells by causing irreparable cellular damage that triggers apoptosis. Consequently, the efficacy of cancer treatments depends not only on the cellular damage they cause but also on the cell's ability to respond to the damage by inducing apoptotic machinery. Accordingly, mutations in apoptotic pathways may result in resistance to drugs and radiation. Such mutations might serve as predictors of chemoresistance and, most importantly, as new treatment targets.

Mitochondria and cell surface receptors mediate the two main pathways …