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

Clin Cancer Res. 2015 May 1;21(9):1995-2000. doi: 10.1158/1078-0432.CCR-14-0858.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Hypoxia / drug effects*
  • Cell Hypoxia / physiology
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology
  • Neoplasms / radiotherapy*
  • Oxygen Consumption / drug effects*
  • Oxygen Consumption / physiology
  • Radiation-Sensitizing Agents / pharmacology*

Substances

  • Radiation-Sensitizing Agents