Strategizing the Clone Wars: Pharmacological Control of Cellular Sensitivity to Radiation

Abstract

The combined administration of ionizing radiation and systemic chemotherapy is an accepted standard of care for numerous cancers. Improved efficacy through the combination of therapies reflects several interrelated processes, including DNA damage, inhibition of DNA synthesis, alteration of cell cycle distribution, and impaired DNA repair. Insights into cellular responses to radiation have led to the use of drugs that target specific intracellular signaling pathways to sensitize cells to radiation. Combinations of chemotherapy and radiation continue to be optimized, based on preclinical and early-phase clinical data that indicate the ideal sequencing of therapies, the best combinations of agents (including radiosensitizers), and the most reliable biological markers for predicting patient responsiveness. This review summarizes our current understanding of radiosensitization as it relates to preclinical drug development and discusses the potential benefits of judiciously incorporating both traditional and targeted chemotherapy into radiation regimens.