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.affiliation: Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
authors.forename: Charlene
authors.initials: C
authors.lastname: Kan
authors.affiliation: Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio. Electronic address: Junran.zhang@case.edu.
authors.forename: Junran
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000502:physiology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000532:radiotherapy*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005819:Genetic Markers; D006801:Humans; D009154:Mutation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use; D011836:Radiation Tolerance / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D005819:Genetic Markers; D000067856:Poly(ADP-ribose) Polymerase Inhibitors