Pharmacology of oxaliplatin and the use of pharmacogenomics to individualize therapy.

摘要: Oxaliplatin is a relatively new platinum analogue that currently used in pharmacotherapy of metastatic colorectal cancer. Its dose-limiting toxicity sensory neuropathy, which can be modulated by infusion calcium and magnesium. exerts its anti-tumour effects platinum-adduct formation, binding to cellular proteins possibly interfering with RNA synthesis as well. If they are not removed from DNA, oxaliplatin adducts lethal. Cellular defense mechanisms prevent adduct formation (e.g., glutathione-S-transferase) or remove DNA nucleotide excision repair). Depending on the activity necessary enzymes these pathways, induced damage varies one individual another. There growing evidence polymorphisms genes coding for repair metabolic inactivation routes contribute interindividual differences efficacy oxaliplatin. Single (SNPs) may yield inactive enzymes, increased gene transcription hence enzyme production. This review covers findings recent investigations associations SNPs clinical outcome after chemotherapy