Chapter 13 - The role of DNA damage and repair in toxicity to postmitotic cells caused by cancer therapies

Abstract

With increased survival rates for cancer patients, toxicity secondary to anticancer therapies has become a prevalent clinical concern. Of major importance are toxicities occurring in postmitotic cells (cardiac muscle, skeletal muscle, and neurons) since these toxicities are quite debilitating, they often persist long after therapy is discontinued, and few interventions exist to prevent or reverse them. Although the mechanisms mediating these toxicities are not known, one promising area that requires further exploration is the ability of DNA repair mechanisms to reverse the toxic effects of a number of anticancer drugs. For example, studies in animal models show that enhancing the base excision repair pathway attenuates neuronal damage by chemotherapeutic agents, suggesting that manipulating DNA repair mechanisms may be a novel approach to diminish neurotoxicity during or after cancer therapy. Whether DNA damage and repair are critical in cardiac and skeletal muscle toxicity after cancer therapy remains to be determined.