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The relative biological effectiveness of proton irradiation in dependence of DNA damage repair

Deycmar, Simon; Faccin, Erica; Kazimova, Tamara; Knobel, Philip A; Telarovic, Irma; Tschanz, Fabienne; Waller, Verena; Winkler, Rona; Yong, Carmen; Zingariello, Dario; Pruschy, Martin (2020). The relative biological effectiveness of proton irradiation in dependence of DNA damage repair. British Journal of Radiology, 93(1107):20190494.

Abstract

Clinical parameters and empirical evidence are the primary determinants for current treatment planning in radiation oncology. Personalized medicine in radiation oncology is only at the very beginning to take the genetic background of a tumor entity into consideration to define an individual treatment regimen, the total dose or the combination with a specific anticancer agent. Likewise, stratification of patients towards proton radiotherapy is linked to its physical advantageous energy deposition at the tumor site with minimal healthy tissue being co-irradiated distal to the target volume. Hence, the fact that photon and proton irradiation also induce different qualities of DNA damages, which require differential DNA damage repair mechanisms has been completely neglected so far. These subtle differences could be efficiently exploited in a personalized treatment approach and could be integrated into personalized treatment planning. A differential requirement of the two major DNA double-strand break repair pathways, homologous recombination and non-homologous end joining, was recently identified in response to proton and photon irradiation, respectively, and subsequently influence the mode of ionizing radiation-induced cell death and susceptibility of tumor cells with defects in DNA repair machineries to either quality of ionizing radiation. This review focuses on the differential DNA-damage responses and subsequent biological processes induced by photon and proton irradiation in dependence of the genetic background and discusses their impact on the unicellular level and in the tumor microenvironment and their implications for combined treatment modalities.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Radiation Oncology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Radiology, Nuclear Medicine and Imaging
Uncontrolled Keywords:Radiology Nuclear Medicine and imaging, General Medicine
Language:English
Date:1 March 2020
Deposited On:13 Feb 2020 16:01
Last Modified:23 Oct 2024 01:36
Publisher:British Institute of Radiology
ISSN:0007-1285
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1259/bjr.20190494
PubMed ID:31687835
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