Different cell thresholds for commitment to death: a link between carcinogenesis and drug resistance.

All classes of anticancer drugs induce apoptosis both in vitro and in vivo. Because apoptosis is a genetically controlled process, this implies that death induced by these drugs is genetically controlled at loci different from those involved in their direct mechanisms of action. This is stimulus-response-coupling; the drugs provide the stimulus through imposition of cell damage. Failure to couple damage to the response of death characterizes a pleiotropic form of drug resistance. Different cell phenotypes have different thresholds for the engagement of death, which need not only be by apoptosis. The balance of expression of genes which promote or suppress active cell death defines these thresholds.