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  • Review Article
  • Published:

Opportunities and challenges of radiotherapy for treating cancer

Nature Reviews Clinical Oncology volume 12, pages 527–540 (2015)Cite this article

Subjects

Key Points

  • Radiotherapy needs a paradigm shift to include biological interventions that are tailored to radiation-related phenomena

  • DNA-repair mechanisms are obvious targets for interventions aimed at improving the radiotherapeutic benefit

  • Chromatin structure and nuclear architecture critically influence the dynamics and extent of DNA damage and repair, and thus the response to radiation

  • Cells exist along a wide spectrum of radiation responsiveness, with cancer stem cells generally being radioresistant

  • Radiation therapy can be an antitumour immune adjuvant and new approaches to immunotherapy will offer the opportunity to exploit this interaction

  • Biomarkers that are redox-related or immune-related might help evaluate the status of patients with cancer and provide insight into how best to combine radiotherapy with biological treatments in each individual

Abstract

The past 20 years have seen dramatic changes in the delivery of radiation therapy, but the impact of radiobiology on the clinic has been far less substantial. A major consideration in the use of radiotherapy has been on how best to exploit differences between the tumour and host tissue characteristics, which in the past has been achieved empirically by radiation-dose fractionation. New advances are uncovering some of the mechanistic processes that underlie this success story. In this Review, we focus on how these processes might be targeted to improve the outcome of radiotherapy at the individual patient level. This approach would seem a more productive avenue of treatment than simply trying to increase the radiation dose delivered to the tumour.

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Figure 1: The effect of the cell-cycle phase on radiosensitivity and on the DNA-repair pathway that is utilized.
Figure 2: Possible mechanisms by which PARP-1 inhibitors might interact with radiation-induced DNA damage for therapeutic benefit.
Figure 3: Redox and how it might influence both radiation responses and the immune system.

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Acknowledgements

The authors would like to dedicate this article to H. Rodney Withers, past Chair of Radiation Oncology at the University of California, Los Angeles (UCLA), who died on 25 February 2015. 'Rod' was an intellectual giant who shaped the discipline of radiobiology as it related to radiotherapy. He is greatly missed. The authors would also like to thank Dr Ekaterini Angelis for editorial assistance. Financial support for the authors came from the US Army MTA W81XWH-11-1-0531 (W.H.M.) and NIAID 2U19 AI067769 (W.H.M.).

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  1. Department of Radiation Oncology, Room B3-109, Center for Health Sciences, Westwood, University of California, Los Angeles (UCLA), Los Angeles, 90095-1714, CA, USA

    Dörthe Schaue & William H. McBride

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Schaue, D., McBride, W. Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol 12, 527–540 (2015). https://doi.org/10.1038/nrclinonc.2015.120

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