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Title: BRCA1 Mutation: A Predictive Marker for Radiation Therapy?

Abstract

DNA repair, in particular, DNA double-strand break (DSB) repair, is essential for the survival of both normal and cancer cells. An elaborate repair mechanism has been developed in cells to efficiently repair the damaged DNA. The pathways predominately involved in DSB repair are homologous recombination and classic nonhomologous end-joining, although the alternative NHEJ pathway, a third DSB repair pathway, could also be important in certain contexts. The protein of BRCA1 encoded by the tumor suppressor gene BRCA1 regulates all DSB repair pathways. Given that DSBs represent the most biologically significant lesions induced by ionizing radiation and that impaired DSB repair leads to radiation sensitivity, it has been expected that cancer patients with BRCA1 mutations should benefit from radiation therapy. However, the clinical data have been conflicting and inconclusive. We provide an overview about the current status of the data regarding BRCA1 deficiency and radiation therapy sensitivity in both experimental models and clinical investigations. In addition, we discuss a strategy to potentiate the effects of radiation therapy by poly(ADP-ribose) polymerase inhibitors, the pharmacologic drugs being investigated as monotherapy for the treatment of patients with BRCA1/2 mutations.

Authors:
;
Publication Date:
OSTI Identifier:
22458775
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 93; Journal Issue: 2; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0360-3016
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; BIOLOGICAL PATHWAYS; DAMAGE; DNA; DNA REPAIR; DRUGS; GENE RECOMBINATION; GENES; MUTATIONS; NEOPLASMS; PATIENTS; PROTEINS; RADIOSENSITIVITY; RADIOTHERAPY; RIBOSE; STRAND BREAKS

Citation Formats

Kan, Charlene, and Zhang, Junran, E-mail: Junran.zhang@case.edu. BRCA1 Mutation: A Predictive Marker for Radiation Therapy?. United States: N. p., 2015. Web. doi:10.1016/J.IJROBP.2015.05.037.
Kan, Charlene, & Zhang, Junran, E-mail: Junran.zhang@case.edu. BRCA1 Mutation: A Predictive Marker for Radiation Therapy?. United States. doi:10.1016/J.IJROBP.2015.05.037.
Kan, Charlene, and Zhang, Junran, E-mail: Junran.zhang@case.edu. Thu . "BRCA1 Mutation: A Predictive Marker for Radiation Therapy?". United States. doi:10.1016/J.IJROBP.2015.05.037.
@article{osti_22458775,
title = {BRCA1 Mutation: A Predictive Marker for Radiation Therapy?},
author = {Kan, Charlene and Zhang, Junran, E-mail: Junran.zhang@case.edu},
abstractNote = {DNA repair, in particular, DNA double-strand break (DSB) repair, is essential for the survival of both normal and cancer cells. An elaborate repair mechanism has been developed in cells to efficiently repair the damaged DNA. The pathways predominately involved in DSB repair are homologous recombination and classic nonhomologous end-joining, although the alternative NHEJ pathway, a third DSB repair pathway, could also be important in certain contexts. The protein of BRCA1 encoded by the tumor suppressor gene BRCA1 regulates all DSB repair pathways. Given that DSBs represent the most biologically significant lesions induced by ionizing radiation and that impaired DSB repair leads to radiation sensitivity, it has been expected that cancer patients with BRCA1 mutations should benefit from radiation therapy. However, the clinical data have been conflicting and inconclusive. We provide an overview about the current status of the data regarding BRCA1 deficiency and radiation therapy sensitivity in both experimental models and clinical investigations. In addition, we discuss a strategy to potentiate the effects of radiation therapy by poly(ADP-ribose) polymerase inhibitors, the pharmacologic drugs being investigated as monotherapy for the treatment of patients with BRCA1/2 mutations.},
doi = {10.1016/J.IJROBP.2015.05.037},
journal = {International Journal of Radiation Oncology, Biology and Physics},
issn = {0360-3016},
number = 2,
volume = 93,
place = {United States},
year = {2015},
month = {10}
}