Targeting Notch to overcome radiation resistance

Oncotarget. 2016 Feb 16;7(7):7610-28. doi: 10.18632/oncotarget.6714.


Radiotherapy represents an important therapeutic strategy in the treatment of cancer cells. However, it often fails to eliminate all tumor cells because of the intrinsic or acquired treatment resistance, which is the most common cause of tumor recurrence. Emerging evidences suggest that the Notch signaling pathway is an important pathway mediating radiation resistance in tumor cells. Successful targeting of Notch signaling requires a thorough understanding of Notch regulation and the context-dependent interactions between Notch and other therapeutically relevant pathways. Understanding these interactions will increase our ability to design rational combination regimens that are more likely to be safe and effective. Here we summarize the role of Notch in mediating resistance to radiotherapy, the different strategies to block Notch in cancer cells and how treatment scheduling can improve tumor response. Finally, we discuss a need for reliable Notch related biomarkers in specific tumors to measure pathway activity and to allow identification of a subset of patients who are likely to benefit from Notch targeted therapies.

Keywords: Notch; Notch inhibitor; personalized treatment; radiotherapy; treatment resistance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Neoplasms / prevention & control*
  • Radiation Tolerance / drug effects*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Receptors, Notch / antagonists & inhibitors*


  • Radiation-Sensitizing Agents
  • Receptors, Notch