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The diversity of cell populations is regulated by extracellular andintracellular variability. The latter includes genetic, epigenetic andstochastic variability, all contributing to the experimentally observedheterogeneity in response to external death-inducing stimuli. Studies ofsources and regulation of variability in commitment to apoptotic cancer celldeath are likely to identify the fundamental features of apoptotic proteinnetworks that are responsible for determining the ultimate cell fate. Systemsbiology approaches, involving computer simulations of the biochemical reactionsaccompanied, if possible, by experimental verification of selected componentsof the model, are proving useful in determining the origins of cell-to-cellvariability in response to external stress stimuli. Here we summarize ourcurrent understanding of the origins of stochastic variability in cells'commitment to apoptosis, and its implications in the field on cancer therapy.

Timing is everything: on the stochastic origins of cell-to-cell variability in cancer cell death decisions