[The biological point of view on pharmacogenetics of anticancer agents in colorectal cancer]

Bull Cancer. 2008 Oct;95(10):935-42. doi: 10.1684/bdc.2008.0728.
[Article in French]

Abstract

Several drugs have been developed and demonstrated similar efficacy in colorectal cancer treatment therefore with choice, time comes for decision. The biologist will have to provide the tools allowing to clarify this choice. Among the tools available, those of pharmacogenetics and pharmacogenomics appear most promising and recent examples allow to illustrate their clinical interest. The pharmacogenetics of anti-cancer agents presents a clinical characteristic, which requires to hold into account the genetic variations not only of host cells but also of those of the tumor cells. Among the most conclusive examples one is that of the prediction of severe neutropenia induced by the irinotecan among patients homozygous for * 28 allele of UGT1A1 enzyme which conjugates SN38 active compound of irinotecan, the other one is the presence of a KRAS mutated allele in tumor cell to predict resistance to anti EGFR antibodies in the treatment of colorectal metastatic cancer.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Camptothecin / analogs & derivatives
  • Camptothecin / metabolism
  • Camptothecin / therapeutic use
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Cyclin D1 / genetics
  • Dihydrouracil Dehydrogenase (NADP) / genetics
  • Dihydrouracil Dehydrogenase (NADP) / metabolism
  • Epidermal Growth Factor / genetics
  • Fluorouracil / metabolism
  • Fluorouracil / therapeutic use
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Humans
  • Irinotecan
  • Mutation / genetics
  • Organoplatinum Compounds / metabolism
  • Organoplatinum Compounds / therapeutic use
  • Polymorphism, Genetic
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptors, IgG / genetics
  • Thymidylate Synthase / genetics
  • Thymidylate Synthase / metabolism
  • ras Proteins / genetics

Substances

  • Antineoplastic Agents
  • FCGR2A protein, human
  • FCGR3A protein, human
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • Receptors, IgG
  • Cyclin D1
  • Epidermal Growth Factor
  • Irinotecan
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Glutathione Transferase
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Fluorouracil
  • Camptothecin