[The biological point of view on pharmacogenetics of anticancer agents in colorectal cancer].
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.
Laurent-Puig
Pierre
P
Université Paris-Descartes, Inserm UMR-S U775 Bases moléculaires de la réponse aux xénobiotiques, Hôpital Européen Georges-Pompidou, Pôle de biologie, Pôle de cancérologie. Pierre.Laurent-Puig@univ-paris5.fr
Lièvre
Astrid
A
Ducreux
Michel
M
Loriot
Marie-Anne
MA
D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000235:genetics; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D009154:Mutation / Q000235:genetics; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D017452:Receptors, IgG / Q000235:genetics; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics; D000099148:UGT1A1 Enzyme
D000970:Antineoplastic Agents; D002166:Camptothecin; D019938:Cyclin D1; D042943:Dihydrouracil Dehydrogenase (NADP); D004815:Epidermal Growth Factor; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D000077146:Irinotecan; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D017452:Receptors, IgG; D013940:Thymidylate Synthase; D018631:ras Proteins; D000099148:UGT1A1 Enzyme; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; C117307:KRAS protein, human