Author: Radwan Ansaar
Ansaar, Radwan, 2024 UDP-Glycosyltransferases (UGTs) in Anti-Cancer Drug Resistance, Flinders University, College of Medicine and Public Health
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Resistance to anti cancer drugs represents a major hurdle in treating breast cancer. This project sought to understand the role of a drug metabolising enzyme called UGT2B7 in mediating resistance to chemotherapy, with a particular focus on the anti-cancer therapy, epirubicin.
Expression of UGT2B7 in breast cancer cells was induced by epirubicin; and in turn, high levels of UGT2B7 induced resistance to this chemotherapy. Thus, UGT2B7 may be a biomarker of drug resistance and also a target for overcoming it.
We further identified a mechanism by which co-administering complementary anti cancer drugs (i.e. tamoxifen or gefitinib) could overcome the adverse effects of high UGT2B7 expression. This mechanism, referred to as pharmaco enhancement, might lead to the development of more effective chemotherapy regimens.
Lastly, using the physiological characteristics of patients, we developed a whole body pharmacokinetic model that can be applied to predict plasma chemotherapy levels. This is a useful tool for determining optimised dosing, potentially paving the way for personalised therapies.
Keywords: UDP-Glycosyltransferase (UGT), UGT2B7, breast cancer, pharmacology, PBPK, drug metabolism, drug disposition, epirubicin, tyrosine kinase inhibitor (TKI), drug-drug interaction (DDI)
Subject: Clinical Pharmacology thesis
Thesis type: Doctor of Philosophy
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Robyn Meech