Targeting PARP for Chemoradiosensitization: Opportunities, Challenges, and the Road Ahead

Abstract

In many patients with cancer, the dose of radiation therapy (RT) that can be safely administered is insufficient to achieve high rates of local tumor control and cure. In others, damage to normal tissues is a concern even at moderate doses. In these settings, RT, or chemoradiation therapy (CRT), ideally would be combined with novel targeted drugs that can enhance the tumoricidal effects of standard therapy but without significantly increased normal tissue toxicity. Over the past decade, major advances in precision medicine have supplied the field of radiation oncology with countless opportunities to enhance the antitumor effects of CRT. However, a large body of preclinical research and clinical investigations on molecular targeted drugs has not yet translated into any meaningful number of combinations of RT or CRT with targeted radiosensitizers that are approved by the US Food and Drug Administration. In fact, to date the epidermal growth factors receptor-directed monoclonal antibody cetuximab remains the only targeted agent approved by the Food and Drug Administration for concurrent administration with RT in head and neck (H&N) cancers. There are considerable challenges to clinical translation of combining targeted drugs with CRT or RT that the field has only recently begun to fully appreciate.