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Nucleotide excision repair pathways involved in Cisplatin resistance in non-small-cell lung cancer

Rafael Rosell1, Miguel Taron, Agusti Barnadas

  • 1Medical Oncology Service, Hospital Germans Trias i Pujol, Barcelona, Spain. rrosell@ns.hugtip.scs.es

Cancer Control : Journal of the Moffitt Cancer Center
|August 14, 2003
PubMed
Abstract

Insights

Genetic markers like ERCC1 mRNA levels may predict chemotherapy response in non-small-cell lung cancer (NSCLC). Further validation is needed to personalize cisplatin treatment for NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Genetic abnormalities in DNA repair pathways influence chemosensitivity in non-small-cell lung cancer (NSCLC).
  • Translational assays for individualized chemotherapy in NSCLC are lacking.
  • Cisplatin-based chemotherapy regimens show limited efficacy in metastatic NSCLC.

Purpose of the Study:

  • To review mechanisms of cisplatin resistance in NSCLC.
  • To investigate the role of nucleotide excision repair (NER) pathways in chemoresistance.
  • To evaluate the potential of ERCC1 as a biomarker for NSCLC treatment response.

Main Methods:

  • Review of principal mechanisms of cisplatin resistance.
  • Focus on nucleotide excision repair (NER) pathways, including transcription-coupled repair and global genomic repair.
  • Analysis of ERCC1 (excision repair cross-complementation group 1) function in DNA repair.

Main Results:

  • ERCC1, a DNA endonuclease, forms a heterodimer with xeroderma pigmentosum complementation group F and incises DNA at cisplatin-DNA adducts.
  • Overexpression of ERCC1 and other NER enzymes is implicated in cisplatin resistance in ovarian and NSCLC.
  • Baseline ERCC1 mRNA overexpression correlates with poor response and survival in cisplatin-treated NSCLC patients.

Conclusions:

  • The evidence for many predictive assays in NSCLC is limited.
  • ERCC1 mRNA levels have been extensively analyzed as a potential biomarker.
  • Prospective clinical trials are necessary to fully validate the impact of ERCC1 in NSCLC treatment.

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