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Prof. Siwanon Jirawatnotai
Associate Professor,
Department of Pharmacology, Siriraj Hospital,
Mahidol University, Thailand;
Deputy Director,
Centre of Research Excellence for Precision Medicine
Abstract:
Cholangiocarcinoma (CCA) is a highly heterogeneous malignancy characterized by intrinsic resistance to standard chemotherapy. To address this challenge, we employed a systems pharmacology approach, utilizing high-content drug screening on patient-derived models to map the landscape of therapeutic response. Beyond identifying static genetic targets, our work elucidates the concept of "acquired vulnerability," where resistance to primary targeted agents paradoxically renders tumor cells susceptible to secondary drugs. We demonstrate that specific drug-induced adaptations create collateral sensitivities—particularly involving cell cycle regulation and apoptotic pathways—that can be exploited through rational sequential therapy. Furthermore, we highlight the potential of drug repurposing strategies, such as the use of SMAC mimetics, to sensitize refractory tumors to standard cytotoxic agents. Collectively, these findings provide a framework for navigating tumor plasticity, shifting the paradigm from "one-size-fits-all" treatment to mechanism-based precision oncology.
Bio:
Prof. Siwanon Jirawatnotai is an Associate Professor at Mahidol University and the Deputy Director of the Centre of Research Excellence for Precision Medicine. An expert in molecular genetics, his research primarily focuses on cholangiocarcinoma (CCA), with particular interest in cell cycle regulators such as Cyclin D-dependent kinase, drug-induced plasticity in cancer stem cells, and synthetic lethality therapies. A former postdoctoral fellow at the Dana-Farber Cancer Institute, he now serves on international tumor boards and editorial bodies for journals such as Frontiers in Oncology, Discover Oncology, Cell Division, etc. His work aims to overcome multidrug resistance and identify novel therapeutic targets for CCA.
Details
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| Venue: |
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Seminar Room 4,
4/F, 3 Sassoon Road,
Pokfulam,
Hong Kong SAR, China
All are welcome
For enquiries, please contact us at esther09@hku.hk
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