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Mien-Chie Hung, PhD
China Medical University
Goal: To improve outcomes in patients with triple negative breast cancer (TNBC) by enhancing response to existing therapies and developing new ones.
Impact: Drs. Hung and Hortobagyi have found that the anti-diabetes drug metformin can be given to patients to enhance the effectiveness of immunotherapy. They have also identified an enzyme that may serve as a biomarker to predict resistance to a specific type of immunotherapy (anti PD-1 and anti PD-L1 immune checkpoint therapy).
What’s next: The team will finalize their proposed study of the mechanisms of resistance to anti PD-1 and anti PD-L1 therapies, which they hope will lead to new treatment strategies for TNBC.
TNBC is an aggressive form of breast cancer that is challenging to treat and is more likely to spread and recur. Immunotherapies have shown some benefit in patients with TNBC, but most receive very little benefit and may suffer severe side effects. Drs. Hung and Hortobagyi are investigating the causes of resistance to PD-L1/PD-1 immune checkpoint therapy, which will allow them to develop effective combination therapies to overcome resistance.
Full Research Summary
Research area: Identifying new strategies for treatment of triple-negative breast cancer (TNBC), which is more aggressive and difficult to treat compared to other types of breast cancer.
Impact: While targeted therapy has been successful in treating several types of breast cancer, it has failed to improve outcomes in those with TNBC. Immunotherapies have shown benefit for some patients in clinical trials, but response is low, and the drugs can cause severe side effects. Drs. Hung and Hortobagyi are investigating the causes of resistance to these therapies, which may lead to alternative approaches to improving response.
Current investigation: The team has been focused on enhancing response to anti-PD-1 and anti-PDL1 therapies, which belong to a class of drugs called immune checkpoint inhibitors. Connections between PD-L1 and its sister molecule, PD1, allow cancer cells to go undetected by the immune system.
What they’ve learned so far: Drs. Hung and Hortobagyi have found that metformin—a commonly used drug to treat type 2 diabetes that has been reported to possess anti-tumor activity—has the potential to increase the efficacy of immunotherapy. They also identified a biomarker that may be able to predict resistance to anti-PD-1/PD-L1 treatment.
What’s next: The team will study a monoclonal antibody they developed that targets glycosylated PD-L1. Glycosylation is a process that attaches portions of sugar molecules to a protein, providing it fuel to grow and spread. Drs. Hung and Hortobagyi’s work has suggested that targeting glycosylated PD-L1 may be a potential strategy to enhance immune checkpoint therapy in TNBC.
Mien-Chie Hung, Ph.D. is the President for China Medical University in Taichung, Taiwan. He was vice president for basic research and professor and chair of the Department of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center. He received undergraduate and graduate degrees from the National Taiwan University and his PhD from Brandeis University. After completing postdoctoral training with Dr. Robert A. Weinberg at the Whitehead Institute/Massachusetts Institute of Technology. Dr. Hung was recruited to MD Anderson in 1986. Dr. Hung is internationally recognized for his studies of signal transduction pathways regulated by tyrosine kinase growth factor receptors, such as EGFR and HER-2/neu, as well as molecular mechanisms of tumorigenesis. He is one of members of Selection Committee for Tang Prize in Biopharmaceutical Science category and 2016 Pezcoller Foundation-AACR Award. Dr. Hung also serves as an editorial member for many journals in cancer research to evaluate quality of submission. Notable, he is one of the founding Editorial Members for Cancer Cell, serves as Editor-in-chief for American Journal for Cancer Research (2015-2017) and Senior Editor for Cancer Research (American Association for Cancer Research, 2018-2021). Dr. Hung was inducted as an Academician of the Academia Sinica in Taiwan in 2002, and was selected as a Fellow in Biological Sciences section, American Association for the Advancement of Science (AAAS Fellow) in 2010. He served as President for the Society of Chinese Bioscientists in America (SCBA) from 2004-2005 and is also the recipient of SCBA’s Presidential Award in 2011 and Lifetime Achievement Award in 2017. In addition, Dr. Hung was awarded with The University of Texas MD Anderson Cancer Center LeMaistre Outstanding Achievement Award in 2011 as well as Faculty Achievement Award in Education (1993) and in Basic Research (1998 & 2017). Dr. Hung is a recipient of prestigious educational awards including 2017 UT System Regents’ Outstanding Teaching Award and John P. McGovern Outstanding Teacher Award University of Texas Health Science Center-Houston. Dr. Hung is the only faculty who receives the latter award four times.