Translation of Targeted Radiation Sensitizers into Clinical Trials

Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. Coinciding with this technological maturation, systemic therapies have been combined with radiation in an effort to improve tumor control. Conventional cytotoxic agents have improved survival in several tumor types but cause increased toxicity due to effects on normal tissues. An increased understanding of tumor biology and the radiation response has led to the nomination of several pathways whose targeted inhibition has the potential to radiosensitize tumor cells with lesser effects on normal tissues. These pathways include those regulating the cell cycle, DNA damage repair, and mitogenic signaling. Few drugs targeting these pathways are in clinical practice, although many are in clinical trials. This review will describe the rationale for combining agents targeting these pathways with radiation, provide an overview of the current landscape in the clinical pipeline and attempt to outline the future steps.