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The Radiobiological Effects of Proton Beam Therapy: Impact on DNA Damage and Repair

Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L3 9TA, UK
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Author to whom correspondence should be addressed.
Cancers 2019, 11(7), 946; https://doi.org/10.3390/cancers11070946
Received: 6 May 2019 / Revised: 11 June 2019 / Accepted: 2 July 2019 / Published: 5 July 2019
(This article belongs to the Special Issue New Developments in Radiotherapy)
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Abstract

Proton beam therapy (PBT) offers significant benefit over conventional (photon) radiotherapy for the treatment of a number of different human cancers, largely due to the physical characteristics. In particular, the low entrance dose and maximum energy deposition in depth at a well-defined region, the Bragg peak, can spare irradiation of proximal healthy tissues and organs at risk when compared to conventional radiotherapy using high-energy photons. However, there are still biological uncertainties reflected in the relative biological effectiveness that varies along the track of the proton beam as a consequence of the increases in linear energy transfer (LET). Furthermore, the spectrum of DNA damage induced by protons, particularly the generation of complex DNA damage (CDD) at high-LET regions of the distal edge of the Bragg peak, and the specific DNA repair pathways dependent on their repair are not entirely understood. This knowledge is essential in understanding the biological impact of protons on tumor cells, and ultimately in devising optimal therapeutic strategies employing PBT for greater clinical impact and patient benefit. Here, we provide an up-to-date review on the radiobiological effects of PBT versus photon radiotherapy in cells, particularly in the context of DNA damage. We also review the DNA repair pathways that are essential in the cellular response to PBT, with a specific focus on the signaling and processing of CDD induced by high-LET protons. View Full-Text
Keywords: DNA damage; DNA repair; proton beam therapy; radiobiology DNA damage; DNA repair; proton beam therapy; radiobiology
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Vitti, E.T.; Parsons, J.L. The Radiobiological Effects of Proton Beam Therapy: Impact on DNA Damage and Repair. Cancers 2019, 11, 946.

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