Novel therapeutics in combination with radiotherapy to improve cancer treatment: rationale, mechanisms of action and clinical perspective.

Our increased understanding of the molecular processes underlying cellular sensitivity to ionizing radiation has led to the identification of novel targets for intervention. New agents have become available for combined use to overcome radioresistance and enhance the clinical efficacy of radiotherapy. This rational selection of potential radiosensitizers contrasts with the empirical approach that has dominated the field of chemo-radiotherapy over the last decades. It allows the identification of those patients who will benefit most from a specific combination by exploiting new predictive biomarkers of response. In this review we present several approaches of targeted radiosensitization and discuss the available in vitro and in vivo results that support their translation into clinical trials. We focus on EGFR-inhibiting, anti-angiogenic, apoptosis-modulating and PARP-interfering strategies.