Background: Programmed cell death involves a genetic reprogramming of the cell to promote an energy-dependent cascade of biochemical and morphological changes within the cell that result in its death and elimination. Methods: The regulations and mechanisms of programmed cell death are reviewed with an emphasis on how derangement of this mechanism may be involved in modulating responsiveness to chemotherapy. Results: Activation of this programmed death process is controlled by a series of endogenous cell-type-specific signals. In addition, a variety of exogenous cell-damaging treatments (eg, radiation, chemicals, and viruses) and most chemotherapeutic drugs can activate this pathway if sufficient injury to the cell occurs. Resistance to chemotherapy can involve alterations in the ability of a malignant cell to activate the programmed cell death (apoptotic) pathway when damaged by these exogenous agents. Conclusion: The most important determinant of tumor resistance may be a generalized resistance to induction of programmed cell death rather than resistance based on specific alteration in drug/target interactions.
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