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Pharmacogenetics of platinum-based chemotherapy in non-small cell lung cancer: predictive validity of polymorphisms

Gerhard Hamilton1, Barbara Rath1

  • 1a Department of Surgery , Medical University of Vienna , Vienna , Austria.

Expert Opinion on Drug Metabolism & Toxicology
|December 12, 2017
PubMed
Abstract

Insights

Single nucleotide polymorphisms (SNPs) in the ERCC1 gene may not reliably predict non-small cell lung cancer (NSCLC) response to platinum chemotherapy. Further research is needed to understand complex cellular processes influencing treatment outcomes.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Platinum-based chemotherapy is a cornerstone treatment for non-small cell lung cancer (NSCLC).
  • Chemoresistance significantly limits the efficacy of platinum drugs, which induce cell death via DNA crosslinks.
  • The nucleotide excision repair (NER) pathway, involving ERCC1 (excision repair cross-complementing 1), repairs these DNA defects.

Purpose of the Study:

  • To summarize and discuss divergent results regarding the predictive power of ERCC1 single nucleotide polymorphisms (SNPs) in NSCLC.
  • To explore the reasons behind contradictory data on ERCC1 SNPs as predictive markers for platinum chemotherapy response.

Main Methods:

  • Review of studies investigating ERCC1 codon 118 C/T and C8092A SNPs for their association with NSCLC chemotherapy response.
  • Analysis of existing literature to identify factors contributing to conflicting findings.

Main Results:

  • ERCC1 SNPs, specifically codon 118 C/T and C8092A, have been extensively studied for their predictive value in NSCLC.
  • Published studies show contradictory results regarding the association between these ERCC1 SNPs and patient response to platinum chemotherapy.

Conclusions:

  • The cytotoxicity of platinum compounds involves complex cellular processes where DNA repair may not be the rate-limiting step.
  • Current evidence suggests that assessing a limited number of DNA repair protein polymorphisms, like ERCC1 SNPs, is not reliably associated with treatment response in NSCLC patients.
  • Factors such as drug combinations, patient heterogeneity, and impaired NER pathways in treated cohorts complicate the predictive utility of ERCC1 SNPs.
Keywords:
ERCC1Non-small cell lung cancercisplatindrug responsepolymorphism

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