title: [DNA repair pathways and non-small cell lung cancer: clinical perspectives].
abstract: The role of DNA repair pathways is to maintain cellular integrity. However, genetic instability is a driving force in the development of tumor cells and many tumors are characterized by the loss of functionality in one or several DNA repair pathways. However, if genetic instability trespasses a certain point, it will induce cell death. Therefore, the dysfunctionality of several DNA repair pathways could represent an Achille's heel for the tumor, if such pathways could be pharmacologically targeted. For instance, the inhibition of PARP1, a protein in the base excision repair pathway (BER) is sufficient to induce cell death in cancer cells bearing BRCA1 or BRCA2 mutations, which are essential proteins in the homologous recombination repair pathway (HR). This phenomenon called "synthetic letality" constitutes recent knowledge and we discuss here the possibility that this strategy might be applied to innovative treatment options in lung cancer. Further, several DNA repair proteins could be used in lung cancer as prognostic and/or predictive biomarkers of response to chemotherapy or radiation. Indeed, specific biomarkers of each DNA repair pathway do exist and could guide oncologists in therapeutic decisions (e.g. ERCC1 and cisplatin). Finally, pharmacologic modulation of DNA repair proteins might also be interesting as it might increase therapeutic efficacy of anticancer strategies (DNA-interacting chemotherapy and radiotherapy). Here, we will present the principal DNA repair pathways and associated biomarkers (ERCC1, MSH2, PARP1 and BRCA1/2), and discuss their status in non-small call lung cancer (NSCLC).
authors: Institut Gustave-Roussy, université Paris-Sud, Inserm U, Villejuif, France. ken.olaussen@igr.fr
authors: Ken André
authors: KA
authors: Olaussen
authors: David
authors: D
authors: Planchard
authors: Julien
authors: J
authors: Adam
authors: Jean-Charles
authors: JC
authors: Soria
mesh_terms: D019313:BRCA1 Protein / Q000502:physiology; D024682:BRCA2 Protein / Q000502:physiology; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D016923:Cell Death / Q000235:genetics; D004260:DNA Repair / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D004720:Endonucleases / Q000502:physiology; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D051718:MutS Homolog 2 Protein / Q000502:physiology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C071447:ERCC1 protein, human; D004720:Endonucleases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein