Pharmacogenetics of taxanes: Impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity

Rafid Salim Jabir, Rakesh Naidu, Muhammad Azrif Bin Ahmad Annuar, Gwo Fuang Ho, Murali Munisamy, Johnson Stanslas

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1979-1988
    Number of pages10
    JournalPharmacogenomics
    Volume13
    Issue number16
    DOIs
    Publication statusPublished - Dec 2012

    Fingerprint

    Taxoids
    Pharmacogenetics
    Pharmacokinetics
    Cytochrome P-450 CYP3A
    Pharmaceutical Preparations
    Genes
    Bile Canaliculi
    Precision Medicine
    Membrane Transport Proteins
    Therapeutics
    Treatment Failure
    Hepatocytes
    Neoplasms
    Survival
    Enzymes
    Proteins

    Keywords

    • ABC
    • ATP-binding cassette
    • breast cancer
    • docetaxel
    • drug transporters
    • paclitaxel
    • pharmacogenetics
    • SLCO1B3
    • SNPs
    • solute carrier organic anion
    • taxanes
    • toxicity

    ASJC Scopus subject areas

    • Pharmacology
    • Genetics
    • Molecular Medicine

    Cite this

    Jabir, R. S., Naidu, R., Annuar, M. A. B. A., Ho, G. F., Munisamy, M., & Stanslas, J. (2012). Pharmacogenetics of taxanes: Impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. Pharmacogenomics, 13(16), 1979-1988. https://doi.org/10.2217/pgs.12.165

    Pharmacogenetics of taxanes : Impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. / Jabir, Rafid Salim; Naidu, Rakesh; Annuar, Muhammad Azrif Bin Ahmad; Ho, Gwo Fuang; Munisamy, Murali; Stanslas, Johnson.

    In: Pharmacogenomics, Vol. 13, No. 16, 12.2012, p. 1979-1988.

    Research output: Contribution to journalArticle

    Jabir, RS, Naidu, R, Annuar, MABA, Ho, GF, Munisamy, M & Stanslas, J 2012, 'Pharmacogenetics of taxanes: Impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity', Pharmacogenomics, vol. 13, no. 16, pp. 1979-1988. https://doi.org/10.2217/pgs.12.165
    Jabir, Rafid Salim ; Naidu, Rakesh ; Annuar, Muhammad Azrif Bin Ahmad ; Ho, Gwo Fuang ; Munisamy, Murali ; Stanslas, Johnson. / Pharmacogenetics of taxanes : Impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity. In: Pharmacogenomics. 2012 ; Vol. 13, No. 16. pp. 1979-1988.
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