Zhen Fan, MD

2008-2009 BCRF Project:
Co-Investigator: John Mendelsohn, MD, The University of Texas MD Anderson Cancer Center, Houston

Drs. Fan and Mendelsohn have a long-term interest in breast cancer research that focuses mainly on understanding the biological roles of the human epidermal growth factor (EGF) receptor (HER) family members and its related proteins in the development, progression, and metastatic spread of breast cancer. Elucidation of the functions of these important cell signal regulatory proteins will enable them to explore new opportunities for selective inhibition of the functions of these proteins, thereby achieving therapeutic effects. HER1 (also known as EGFR) and HER2, each expressed in approximately 20-30% breast cancer, are two closely related cell transmembrane receptors belonging to the same HER family and activate basically overlap downstream cell signaling.

It is noteworthy, however, that the clinical outcome resulting from targeting these two proteins with drugs (monoclonal antibodies or small molecule inhibitors) are quite different. The response of patients to HER2-targeted therapy is both clinically and statistically correlated with the levels of HER2 expression whereas the response to EGFR-targeted therapy has not shown a definitive link to the level of EGFR expression. The reason of this discrepancy between HER1 and HER-targeted therapy is largely unknown.

In 2008-2009, the researchers will address this discrepancy in part by focusing our study on a protein, called breast tumor kinase (Brk), for its potential role in adversely affecting breast cancer responses to the EGFR-targeted therapy. Results from these studies should justify the development of novel anti-Brk drugs to use together with EGFR-targeted therapies. The researchers expect that the knowledge generated from this research will be of great value in the clinical management of breast cancer.

Bio:
Zhen Fan was awarded his medical degree in 1985 from the Medical School of Shanghai Medical University, one of the most prestigious medical schools in China. In 1988, Dr. Fan completed additional studies at the Graduate School of the same university. He served medical residency at Zhong Shan Hospital of Shanghai Medical University from 1988 to 1991. In 1991, he joined Dr. John Mendelsohn's laboratory as a postdoctoral research fellow at Memorial Sloan-Kettering Cancer Center in New York City, focusing on studies of the epidermal growth factor (EGF) receptor as a target for cancer therapy. From 1994 to 1995, he was a Research Associate in the Program of Molecular Pharmacology and Therapeutics; in 1996, he joined the faculty as an Assistant Molecular Biologist in the Department of Medicine, Memorial Sloan-Kettering Cancer Center. In late 1996, Dr. Fan moved to Houston and joined the faculty of The University of Texas, M. D. Anderson Cancer Center. He is currently associate professor of medicine and directs an independent laboratory in the Department of Experimental Therapeutics.

Dr. Fan has made considerable contributions to our understanding of the mechanism and development of the EGF receptor monoclonal antibody C225 (also known as ERBITUX) as a novel anticancer agent. C225 is now a leading drug candidate for inhibiting EGF receptor function in human cancer. He and his colleagues demonstrated that C225 can exert additive or even synergistic cytotoxic effects against well-established human tumor xenografts growing in athymic (nude) mice when administered concurrently with chemotherapeutic agents or radiation therapy. These seminal studies provided the impetus and preclinical rationale for the ongoing clinical phase II and III trials with C225 in combination with chemotherapy and/or radiation therapy in cancer patients.

Dr. Fan's current research interests focus on identification and validation of new cancer targets involved in growth factor receptor-mediated signal transduction pathways. He hopes to find better cancer molecular therapeutic approaches for potential clinical applications, particularly, in breast cancer patients.