Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
The diversity of cell populations is regulated by extracellular and intracellular variability. The latter includes genetic, epigenetic and stochastic variability, all contributing to the experimentally observed heterogeneity in response to external death-inducing stimuli. Studies of sources and regulation of variability in commitment to apoptotic cancer cell death are likely to identify the fundamental features of apoptotic protein networks that are responsible for determining the ultimate cell fate. Systems biology approaches, involving computer simulations of the biochemical reactions accompanied, if possible, by experimental verification of selected components of the model, are proving useful in determining the origins of cell-to-cell variability in response to external stress stimuli. Here we summarize our current understanding of the origins of stochastic variability in cells' commitment to apoptosis, and its implications in the field on cancer therapy.