The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

Nat Rev Cancer. 2015 Jul;15(7):409-25. doi: 10.1038/nrc3958.


Radiotherapy plays a central part in curing cancer. For decades, most research on improving treatment outcomes has focused on modulating radiation-induced biological effects on cancer cells. Recently, we have better understood that components within the tumour microenvironment have pivotal roles in determining treatment outcomes. In this Review, we describe vascular, stromal and immunological changes that are induced in the tumour microenvironment by irradiation and discuss how these changes may promote radioresistance and tumour recurrence. We also highlight how this knowledge is guiding the development of new treatment paradigms in which biologically targeted agents will be combined with radiotherapy.

Publication types

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

MeSH terms

  • Animals
  • Cell Hypoxia
  • Fibroblasts / physiology
  • Humans
  • Immune Tolerance
  • Neoplasm Recurrence, Local / etiology*
  • Neoplasms / immunology
  • Neoplasms / radiotherapy*
  • Radiation Tolerance*
  • Transforming Growth Factor beta / physiology
  • Tumor Microenvironment*
  • Vascular Endothelial Growth Factor A / physiology


  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A