Zhen Fan, MD

2007-2008 BCRF Project:
Co-Investigator: John Mendelsohn, MD, The University of Texas MD Anderson Cancer Center, Houston

Recombinant erythropoietin (EPO) is a bioactive protein drug currently used in the clinic for alleviating cancer- or cancer chemotherapy-related anemia and fatigue in cancer patients, including breast cancer patients, owing to its effects on stimulating the production of red blood cells by prolonging the survival of their precursors in the bone marrow.

Controversy has arisen recently as some emerging evidence suggested that certain breast cancer cells also express EPO receptors (the specific cell membrane proteins through which the biologic information of EPO is transmitted into cells). Recombinant EPO may act on breast cancer cells and red blood cell precursors in a similar way. Therefore, recombinant EPO may protect breast cancer cells from various cytotoxic treatments by activating the receptor of EPO in breast cancer cells and, as a result, prolonging breast cancer cell survival.

Over the past year, Drs. Fan and Mendelsohn focused on demonstration of specific cell signaling activated by EPO in breast cancer cells, and evaluated the extent to which EPO plays a negative role in breast cancer responses to trastuzumab treatment. It is expected that successful completion of the planned studies will provide important guidance as to whether recombinant EPO is safe to be used concurrently with trastuzumab for HER2-positive breast cancer patients whose tumors are also positive for the receptor of EPO. This is a very important issue, and the knowledge generated from this research will be of great value to the clinical management of breast cancer and will ultimately benefit patients.

Mid-Year Progress Report:
Resistance of some HER2-overexpressing breast cancer patients to Herceptin (an antibody drug approved for treating patients with HER2-positive breast cancer) remains a challenge in clinical practice. BCRF finding enabled the Fan/Mendelsohn research team to address this challenge by exploring whether concurrent administration of erythropoietin (a drug frequently used in the clinics to treat chemotherapy-induced anemia and fatigue in cancer patients) has a role in causing poor responses of some breast cancer patients to Herceptin.

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.