Interaction of radiation therapy with molecular targeted agents

The development of molecular targeted therapeutics in oncology builds on many years of scientific investigation into the cellular mechanics of malignant transformation and progression. The past two decades have brought an accelerating pace to the clinical investigation of new molecular targeted agents, particularly in the setting of metastatic disease. The integration of molecular targeted agents into phase III clinical trial design has lagged in the curative treatment setting, particularly in combination with established therapeutic modalities such as radiation. In this review, we discuss the interaction of radiation and molecular targeted therapeutics. The dynamics of cellular and tumor response to radiation offer unique opportunities for beneficial interplay with molecular targeted agents that may go unrecognized with conventional screening and monotherapy clinical testing of novel agents. By using epidermal growth factor receptor (EGFR) as a primary example, we discuss recent clinical studies that illustrate the potential synergy of molecular targeted agents with radiation and highlight the clinical value of such interactions. For various molecular targeted agents, their greatest clinical impact may rest in combination with radiation, and efforts to facilitate systematic investigation of this approach appear highly warranted.