Mien-Chie Hung, PhD
Chair and Professor, Department of Molecular and Cellular Oncology
Director, Breast Cancer Basic Research Program
University of Texas MD Anderson Cancer Center
2013-2014 BCRF Project:
(The J.C. Penney Award)
Co-Investigator: Gabriel N. Hortobagyi, MD, University of Texas MD Anderson Cancer Center
With BCRF support, Drs. Hortobagyi and Hung have identified three molecular targets (PKCα, MET and CDK6) and signaling pathways (mTORC/S6K1 and Gli1) that may contribute to triple negative breast (TNBC) cancer progression and may predict overall survival of patients with TNBC. In addition, using drugs that individually inhibit the three identified molecular targets, Drs. Hortobagyi and Hung found that combining any two of the three inhibitors will better inhibit cell growth of triple negative breast cancer cells than each inhibitor alone. In 2013-2014, this team will build on their findings to develop additional novel therapies for women with triple negative breast cancer.
The researchers have identified an optimal combination (combination index) and successfully examined key biological functions in cell culture systems by combinatorial therapies of kinase inhibitors. A manuscript detailing the work is ready to be submitted. Their finding will provide a means to develop effective rational combinatorial therapy of kinase inhibitors for triple negative breast cancer.
Dr. Mien-Chie Hung is Professor and Chair for the Department of Molecular and Cellular Oncology at the University of Texas MD Anderson Cancer Center, Houston, Texas. He received his undergraduate and graduate degrees from the National Taiwan University in Taiwan and his PhD from Brandeis University in Massachusetts. Currently, he also serves as the Director of the Breast Cancer Basic Research Program and is the Ruth Legett Jones Distinguished Chair. In addition, he is Professor, Department of Surgical Oncology, Distinguished Teaching Professor, and Director, Center for Biological Pathways.
Dr. Hung became a member of the Academia Sinica in Taiwan in July, 2002. Dr. Hung serves as a founding Editorial Members on Cancer Cell as well as an Associate Editor on Cancer Research, Clinical Cancer Research, Molecular Cancer Research and Molecular Carcinogenesis.
In recent years, Dr. Hung's laboratory has focused on signaling transduction pathways of tyrosine kinase growth factor receptors such as EGFR and HER-2/neu; molecular mechanisms of oncogenes -including transformation and tumorigenesis; and molecular mechanisms of tumor suppressor genes-mediated anti-tumor activities. His group made a critical breakthrough in showing that the transmembrane tyrosine kinase receptor EGFR can bind to a specific DNA sequence in the nucleus and that it functions as a transcription factor that can activate genes required for cell proliferation. Dr. Hung's group also demonstrated regulation of the cell cycle inhibitor p21 by the HER2/neu oncogene through phosphorylation of p21 by Akt, which results in changes in the subcellular localization.
The study provides a rationale for a long puzzling question surrounding p21--a cell cycle inhibitor that also associates with anti-apoptotic function. Furthermore, his group has demonstrated that an oncogene such as HER2/neu can suppress expression of the tumor suppressor gene p53 through the Akt/MDM2 pathways. The study provides a plausible mechanism showing that the p53 tumor suppressor gene, even without mutation, is frequently silent in oncogene-activated cancer cells such as HER-2/neu and Akt.
Most recently in the April 16th issue of Cell journal, Dr. Hung and co-workers have identified an important new tumor suppressor protein, FOXO3a (known as a longevity gene in some animal models) and a new oncogene, IKK (belongs to a family of enzymes called kinase) that provide targets for cancer therapy. Previously, these proteins had been suspected to be involved in cancer, but there was no direct evidence for that. Dr. Hung has demonstrated that IKK promotes tumorigenesis through inhibition of FOXO3a.
The other main research in Dr. Hung's laboratory is in cancer gene therapy that includes development of preclinical gene therapy animal models, including breast, ovarian and pancreatic cancers; identification of therapeutic genes suitable for cancer gene therapy; and development of gene delivery system for cancer gene therapy. Dr. Hung is the first person to demonstrate that adenovirus 5 E1A gene has anti-tumor ability in HER2/neu-over-expressing cancer cells by downregulation of HER2/neu overexpression. He is also a key person to actively drive laboratory research of E1A tumor suppressor gene into clinical trials (bench to bedside). Furthermore, Dr. Hung's laboratory is working on developing a tumor-targeted nonviral gene delivery system for human cancers such as breast, ovary, pancrease and prostate.