Targeting DNA repair for precision radiotherapy: Balancing the therapeutic ratio

Osman Mahamud; Jonathan So; Melvin L K Chua; Robert G Bristow

doi:10.1016/j.currproblcancer.2017.04.002

Targeting DNA repair for precision radiotherapy: Balancing the therapeutic ratio

Curr Probl Cancer. 2017 Jul-Aug;41(4):265-272. doi: 10.1016/j.currproblcancer.2017.04.002. Epub 2017 Apr 25.

Authors

Osman Mahamud¹, Jonathan So², Melvin L K Chua³, Robert G Bristow⁴

Affiliations

¹ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
² Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
³ Division of Radiation Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, 169610.
⁴ Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada. Electronic address: Rob.bristow@rmp.uhn.on.ca.

PMID: 28641873
DOI: 10.1016/j.currproblcancer.2017.04.002

Abstract

Genomic instability is underpinned by defects in the DNA damage response and DNA repair pathways. Subsequent clonal selection and adaption can lead to a mutator phenotype and tumor aggression. Importantly, tumor cell sensitivity to chemotherapy and radiotherapy can depend highly on the cellular capacity to repair DNA damage within and between tumor types. Annotation of functional defects in DNA damage response and DNA repair function may allow for the development of novel prognostic biomarkers. This information could also be used to predict therapeutic response, including predicting responses following inhibition of DNA repair. Herein, we highlight the increasing potential for annotating and targeting DNA repair defects in patients undergoing precision radiotherapy.

Keywords: DNA repair; Genomics; Precision radiotherapy; Predictive biomarker; Prognostic biomarker; Prostate cancer; Radiosensitizing; Synthetic lethality.

Publication types

Review