Abstract:
:Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
journal_name
Pharmacogenomicsjournal_title
Pharmacogenomicsauthors
Jabir RS,Naidu R,Annuar MA,Ho GF,Munisamy M,Stanslas Jdoi
10.2217/pgs.12.165subject
Has Abstractpub_date
2012-12-01 00:00:00pages
1979-88issue
16eissn
1462-2416issn
1744-8042journal_volume
13pub_type
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