title: DNA damage repair in breast cancer and its therapeutic implications.
abstract: The DNA damage response (DDR) involves the activation of numerous cellular activities that repair DNA lesions and maintain genomic integrity, and is critical in preventing tumorigenesis. Inherited or acquired mutations in specific genes involved in the DNA damage response, for example the breast cancer susceptibility genes 1/2 (BRCA1/2), phosphatase and tensin homolog (PTEN) and P53 are associated with various subtypes of breast cancer. Such changes can render breast cancer cells particularly sensitive to specific DNA damage response inhibitors, for example BRCA1/2 germline mutated cells are sensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. The aims of this review are to discuss specific DNA damage response defects in breast cancer and to present the current stage of development of various DDR inhibitors (namely PARP, ATM/ATR, DNA-PK, PARG, RECQL5, FEN1 and APE1) for breast cancer mono- and combination therapy.
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Reem
authors.initials: R
authors.lastname: Ali
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Emad A
authors.initials: EA
authors.lastname: Rakha
authors.affiliation: Academic Unit of Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Oncology, Nottingham University Hospitals, Nottingham, United Kingdom.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Madhusudan
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Medical School Sheffield Cancer Research Centre, University of Sheffield, Sheffield, United Kingdom. Electronic address: h.bryant@sheffield.ac.uk.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Bryant
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics
chemical_list: D011065:Poly(ADP-ribose) Polymerases
keywords: DDR; DNA damage response; breast cancer; defects; therapeutic implications