Nucleotide excision repair and response and survival to chemotherapy in colorectal cancer patients

Pharmacogenomics. 2016 May;17(7):755-94. doi: 10.2217/pgs-2015-0017. Epub 2016 May 16.

Abstract

Several new chemotherapeutic agents have become available for the treatment of colorectal cancer, which has led to increased complexity in treatment planning. Treatment decision making for individual patients could be facilitated if guided by predictive and prognostic markers. As most cytotoxic drugs induce DNA damage, the DNA damage repair pathways hold potential for yielding such biomarkers. Here, we review the current evidence of a possible involvement of the nucleotide excision repair pathway in the efficacy of chemotherapeutic agents used in the treatment of colorectal cancer. Although a large number of studies have been conducted, they are generally of moderate size and heterogeneous in design. Up to date no firm conclusions can be drawn to translate these results into the clinic. We recommend further comprehensive investigations of the nucleotide excision repair pathway in large patient studies that include both discovery and validation cohorts.

Keywords: 5-fluorouracil; ERCC1; ERCC2; chemotherapy; colorectal cancer; irinotecan; nucleotide excision repair; oxaliplatin; prognostic markers.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • DNA Repair / drug effects*
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Endonucleases / genetics
  • Endonucleases / metabolism
  • Fluorouracil / pharmacology
  • Genetic Markers
  • Humans
  • Irinotecan
  • Organoplatinum Compounds / pharmacology
  • Oxaliplatin
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants
  • Polymorphism, Single Nucleotide
  • Xeroderma Pigmentosum Group D Protein / genetics
  • Xeroderma Pigmentosum Group D Protein / metabolism

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Genetic Markers
  • Organoplatinum Compounds
  • Oxaliplatin
  • Irinotecan
  • ERCC1 protein, human
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human
  • Fluorouracil
  • Camptothecin