Current and emerging strategies to increase the efficacy of ionizing radiation in the treatment of cancer.

Introduction: Ionizing radiation (IR) is an important therapeutic modality used in approximately 50% of all cancer patients and is particularly effective against solid tumors that cannot be removed by surgery or that are refractory to standard anticancer agents. IR is often combined with other chemotherapeutic agents with the goal of sensitizing cancer cells to the cytotoxic effects of IR to produce a synergistic cell-killing effect.

Areas Covered: This review article describes current and emerging therapeutic agents that are designed to increase the therapeutic efficacy of IR. This includes a discussion of how IR causes cell death by damaging nucleic acid. The involvement of various DNA repair pathways, cell-cycle-dependent kinases and apoptotic pathways is also described. This mechanistic information provides the framework to understand how combining therapeutic modalities with IR produces synergistic effects as well as to explain how emerging therapeutic strategies are being designed to inhibit or activate these pathways. Biochemical mechanisms and clinical applications of these chemical entities are discussed. Finally, brief descriptions are provided for several emerging chemical entities that show promise as potential adjunctive agents to sensitize cells to the effects of IR.

Expert Opinion: Using DNA damaging agents or kinase inhibitors to potentiate the cytotoxic effects of IR has significantly improved patient outcomes. However, several advancements in instrumentation as well as new molecular targets are changing the landscape of applying IR as a therapeutic modality.