[Pharmacogenetics of anti-cancer drugs]

Abstract

Toxic side-effects of cytotoxic drugs is a stumbling-block of chemotherapy due to the fact that their therapeutic index is narrow. New approaches are necessary to individualize the treatments. Pharmacogenetic analysis is facilitated by easy access to the patient genome via simple blood samples, by the large number of known genes of interest coding for drugs targets or metabolism enzymes and by the fact that their polymorphism (SNP) is often known. Presently more focused on the prevention of toxic side-effects, pharmacogenetics already provides a good deal of confirmed data for clinical applications, such as the detection of dihydropyrimidine dehydrogenase deficiency by sequencing, or UGT1A1 7/7 genotype detection in Gilbert's syndrome for the prevention of 5-FU and irinotecan-induced severe toxicities. It must be emphasized that a SNP which is deleterious for enzyme activity is rarely a contraindication for the drug, provided that some precautions are taken and appropriate therapeutic advice is given by experts.