title: The role of DNA repair pathways in cisplatin resistant lung cancer.
abstract: Platinum chemotherapeutic agents such as cisplatin are currently used in the treatment of various malignancies such as lung cancer. However, their efficacy is significantly hindered by the development of resistance during treatment. While a number of factors have been reported that contribute to the onset of this resistance phenotype, alterations in the DNA repair capacity of damaged cells is now recognised as an important factor in mediating this phenomenon. The mode of action of cisplatin has been linked to its ability to crosslink purine bases on the DNA, thereby interfering with DNA repair mechanisms and inducing DNA damage. Following DNA damage, cells respond by activating a DNA-damage response that either leads to repair of the lesion by the cell thereby promoting resistance to the drug, or cell death via activation of the apoptotic response. Therefore, DNA repair is a vital target to improving cancer therapy and reduce the resistance of tumour cells to DNA damaging agents currently used in the treatment of cancer patients. To date, despite the numerous findings that differential expression of components of the various DNA repair pathways correlate with response to cisplatin, translation of such findings in the clinical setting are still warranted. The identification of alterations in specific proteins and pathways that contribute to these unique DNA repair pathways in cisplatin resistant cancer cells may potentially lead to a renewed interest in the development of rational novel therapies for cisplatin resistant cancers, in particular, lung cancer.
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and Trinity College Dublin, Dublin 8, Ireland. Electronic address: shaneogrady@rcsi.ie.
authors.forename: Shane
authors.initials: S
authors.lastname: O'Grady
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and Trinity College Dublin, Dublin 8, Ireland; Department of Histopathology, St James's Hospital and Trinity College Dublin, Ireland. Electronic address: Stephen.Finn@tcd.ie.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Finn
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and Trinity College Dublin, Dublin 8, Ireland. Electronic address: scuffe@stjames.ie.
authors.forename: Sinead
authors.initials: S
authors.lastname: Cuffe
authors.affiliation: Cancer and Ageing Research Program, Queensland University of Technology, Brisbane, Australia. Electronic address: derek.richard@qut.edu.au.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Richard
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and Trinity College Dublin, Dublin 8, Ireland; Cancer and Ageing Research Program, Queensland University of Technology, Brisbane, Australia. Electronic address: k.obyrne@qut.edu.au.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.affiliation: Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St James's Hospital and Trinity College Dublin, Dublin 8, Ireland. Electronic address: mbarr@stjames.ie.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Barr
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004268:DNA-Binding Proteins; D011065:Poly(ADP-ribose) Polymerases; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin
keywords: Cisplatin; DNA repair; Lung cancer; Resistance