报告题目:Marker-guided effective therapy (Mget)
报告人:洪明奇 院士
主持人:冯新华 教授
时 间:2024年12月23日(周一)下午4点
地 点:校友楼紫金港厅
报告人简介:
Mien-Chie Hung, Ph.D. is the President for China Medical University in Taiwan. He was vice president for basic research, and held a Distinguished Endowed Chair of the Department of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center. He is a basic scientist with a keen translational vision and especially his recent research effort has significantly contributed to understanding the biology of cancer and to developing combinational cancer therapies to overcome resistance. He has published more than 660 peer-reviewed articles. His lifetime h-index reaches to 174 (Google Scholar) and 152 (Scopus), respectively. He is one of members of Selection Committee for Tang Prize in Biopharmaceutical Science category and is one of the founding Editorial Members for Cancer Cell (2002-2020), serves as Molecular Cell Advisory Board Member (2020-present); Cancer Research Senior Editor (2018-2021); American Journal for Cancer Research (AJCR) Editor-in-Chief (2015-2017; 2020-present); Cancer and Metastasis Reviews Editor (2018-present), Cancer Letters Senior Editor (2024-present), etc. Dr. Hung was selected as an Academician of the Academia Sinica in Taiwan in 2002, elected as a Fellow in the Biological Sciences section of the American Association for the Advancement of Science (AAAS) in 2010, and later honored as an Academician of The World Academy of Sciences (TWAS) for the Advancement of Science in Developing Countries in 2023. His research interests are focused on: 1) Elucidation of non-canonical signal pathways of Receptor Tyrosine Kinases and novel posttranslational modifications that play critical roles in tumor progression; 2) Identification of crosstalk signaling pathways to understand drug resistance mechanisms for targeted therapy then develop novel biomarkers and effective therapy to overcome drug resistance; 3) Development of effectively immunotherapy and study of resistant mechanisms of immunotherapy.
Abstract:
Cancer therapy has moved into a new era, including mechanism-driven marker-guided target therapy and immune therapy. Anti-PD-1/PD-L1 therapy is a promising immune therapy for multiple cancer types. Glycosylation of PD-L1 is required for its protein stability and interaction with PD-1 (Nature Comm 2016). Impressive therapeutic effect of developed glycosylation-specific PD-L1 mAb was observed through antibody-drug-conjugate approach (Cancer Cell 2018a & Cancer Res 2020). Through identifying potential targets, we developed marker-guided effective therapy (Mget) to enhance therapeutic efficacy and/or overcome drug resistance by combination therapy with immune checkpoint therapy, including metformin (Mol Cell 2018), c-MET inhibitors (Gastroenterology 2019); and targeting IL-6/JAK1 pathway (J Clin Invest 2019), Galectin-9 (Nature Comm 2021, IJBS 2023a), Tyro 3 (J Clin Invest 2021). Several PARP inhibitors have been approved to treat cancer patients with BRCA mutation and/or homologous recombination defective tumors, we also investigate the mechanisms inducing resistance to PARP inhibitors and develop marker-guided combination therapy to overcome the resistance. The goal is to use identified markers to stratify patients for the right combination therapy. These include reports on c-Met, ALK and GSDMC (Nature Medicine 2016; Nature Cancer 2022 & JCI 2024). This talk will also include our discoveries on novel therapy overcoming resistance to EGFR TKI in lung cancer (Cancer Cell 2018b , clinical trial, NCT06071013 is ongoing ) and other caner types as well as a new methodology to retrieve antigen by protein de-glycosylaton that improves predictive ability of PD-L1 as a biomarker for immunotherapy. (Cancer Cell 2018b, Cancer Cell 2018c, Cancer Cell 2019, AJCR 2022a, Nature Reviews Clinical Oncology 2022, Nature, 2020, Nat. Cell Biol 2020; Mol Cell 2021, IJBS 2023a,b,c, Nature Comm 2024). We will also share with our recent unpublished data for markers-guided effective therapy using novel serum markers (ChiCTR2100054794, submitted). All efforts are focused on mechanism-driven marker-guided effective therapy in a hope to benefit cancer patients.