Molecular Pathways: A Novel Approach to Targeting Hypoxia and Improving Radiotherapy Efficacy via Reduction in Oxygen Demand

Tumor hypoxia presents a unique therapeutic challenge in the treatment of solid malignancies. Its presence has been established to be a poor prognostic factor in multiple cancer types, and past hypoxia-directed approaches have yielded generally disappointing results. Previous approaches have centered on either increasing oxygen delivery or administering agents that preferentially radiosensitize or kill hypoxic cells. However, a novel and potentially more effective method may be to increase therapeutic benefit by decreasing tumor oxygen consumption via agents such as metformin or nelfinavir in a patient population that is enriched for tumor hypoxia. This promising approach is currently being investigated in clinical trials and the subject of this article. (C) 2015 AACR.