Zhen Fan, MD

2012-2013 BCRF Project:
Thanks to the support of The Breast Cancer Research Foundation, Dr. Fan’s team has been exploring a novel cell signaling pathway through which HER2 positive (HER2+) breast cancer cells proliferate and metastasize. They have focused on the impact of breast tumor kinase (Brk), which is highly expressed in approximately two-thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. To elucidate the role of Brk in breast cancer development, progression, and metastasis, Dr. Fan’s group generated several lines of transgenic laboratory models that over-express Brk. They are in the process of characterizing the phenotypes of these transgenic models. Their findings may lead to development of new drugs for breast cancer treatment.

Mid-year Progress: Continuing their project on understanding the genetics of breast cancer development, Dr. Fan and colleagues have gained important knowledge about how the Brk protein interacts with HER2, another important protein involved in breast cancer formation, at cellular and genetic levels. During the current grant period, Dr. Fan's team is focusing on two directions: one is to study biochemical interaction in cell signaling level between the two molecules, and other is to study their interaction in vivo in transgenic laboratory models. The cell signaling work involves examining and analyzing HER2 and Brk protein expression in a panel of 17 breast cancer cell lines and MCF-10A nonmalignant cells. Preliminary findings from the second component of the project working with laboratory models suggest that Brk alone, similar to several other key molecules such as Akt, Src, although they play very important roles in tumorigenesis, may not be tumorigenic alone.

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.