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Title: Pharmacogenetics of Doxorubicin in Asian Breast Cancer Patients
Keywords: Pharmacogenetics, Doxorubicin, Asian Breast Cancer Patients
Issue Date: 3-Sep-2008
Citation: SUMAN LAL CHIRAMMAL SUGUNAN (2008-09-03). Pharmacogenetics of Doxorubicin in Asian Breast Cancer Patients. ScholarBank@NUS Repository.
Abstract: The thesis aimed to comprehensively evaluate the pharmacogenetics of the regulatory nuclear receptor Pregnane-X Receptor (PXR), influx (SLC22A16) and efflux drug transporters (ABCB1, ABCG2, ABCC5, ABCB5 and RLIP76) and drug metabolizing enzymes (CBR1, CBR3) across the biochemical pathway of doxorubicin in Asian breast cancer patients receiving doxorubicin based adjuvant chemotherapy. The study showed that functional polymorphisms in the PXR (*1B haplotype), ABCB1 (linked 1236CC-2677GG-3435CC genotypes), ABCC5 (c.-1679T), SLC22A16 (c.146A>G) and CBR1 (D2 diplotype) genes may significantly contribute to the heterogeneity in doxorubicin disposition among Asian breast cancer patients. It is conceivable that the observed polygenic influence on doxorubicin pharmacogenetics may also influence efficacy of doxorubicin in patients receiving adjuvant chemotherapy. Development and independent validation of multi-compartmental pharmacokinetic-pharmacodynamic models that succinctly incorporate both genetic and non-genetic factors will be invaluable in definitively establishing the clinical utility of findings in the present study on doxorubicin pharmacogenetics.
Appears in Collections:Ph.D Theses (Open)

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