title: Nucleotide excision repair pathways involved in Cisplatin resistance in non-small-cell lung cancer.
abstract: BACKGROUND
  In spite of the growing list of genetic abnormalities identified as being involved in DNA repair pathways that alter chemosensitivity in non-small-cell lung cancer (NSCLC) patients, translational assays have not yet been developed for use in individualized chemotherapy.
  
  
  METHODS
  In metastatic NSCLC, no single cisplatin-based chemotherapy regimen has been shown to be superior to any other. Although these studies show a small survival tail at 3 years, the majority of patients had a median survival of 8 to 10 months. We review the principal mechanisms of cisplatin resistance, particularly those involved in the nucleotide excision repair (NER) pathways (transcription-coupled repair and global genomic repair).
  
  
  RESULTS
  ERCC1 is a single-stranded DNA endonuclease that forms a tight heterodimer with xeroderma pigmentosum complementation group F. It incises DNA on the 5' side of a lesion such as cisplatin-DNA adduct. Therefore, overexpression of ERCC1 and other NER enzymes during ovarian cancer chemotherapy with cisplatin appears to be implicated in the formation of cellular and clinical drug resistance. Recently, baseline ERCC1 mRNA overexpression has been related to poor response and survival in cisplatin-treated NSCLC patients.
  
  
  CONCLUSIONS
  The level of evidence for many assays is limited, and only ERCC1 mRNA levels have been analyzed extensively. The impact of ERCC1 should be fully validated in prospective clinical trials.
authors.affiliation: Medical Oncology Service, Hospital Germans Trias i Pujol, Barcelona, Spain. rrosell@ns.hugtip.scs.es
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Miguel
authors.initials: M
authors.lastname: Taron
authors.forename: Agusti
authors.initials: A
authors.lastname: Barnadas
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.forename: Carme
authors.initials: C
authors.lastname: Sarries
authors.forename: Barbara
authors.initials: B
authors.lastname: Roig
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004260:DNA Repair; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004720:Endonucleases; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms; D011506:Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D011506:Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin