Weizhou Zhang, Ph.D., a professor in the department of pathology, immunology & laboratory medicine in the University of Florida College of Medicine, has received a $2.5 million R01 grant from the National Cancer Institute to study a novel therapeutic strategy to treat renal clear cell carcinomas.
Renal cell carcinomas are among the 10 most common cancer types in men and women worldwide. Most are clear cell carcinomas, an atypical type of cancer that is often resistant to traditional therapeutics.
In previous research, Zhang’s team found that tumor-induced regulatory T cells may be the major cells involved in suppressing the body’s immune response to fight cancer. They found that two drugs targeting BCL-XL proteins were effective at eliminating these cells and activating immunity against tumors.
In the current project, Zhang’s team will establish that senescent regulatory T cells — those that aid tumor development in the process of aging — are a therapeutic target for renal clear cell carcinoma. They will test this by using Proteolysis targeting chimera, or PROTAC, technology, which kills tumor-infiltrating regulatory T cells by degrading the pro-survival BCL-XL protein.
Using in vivo models and cancer specimens, Zhang’s team will assess the efficacy of targeting BCL-XL by combining it with other frontline therapeutics. This work will provide a rationale for targeting BCL-XL for cancer immunotherapy treatment for renal cell carcinomas.
Zhang, who holds the Dr. and Mrs. James Robert Spencer Professorship of Pathology, is a member of the Cancer Center’s Mechanisms of Oncogenesis research program. The team also includes Guangrong Zheng, Ph.D., an associate professor in the department of medicinal chemistry in the UF College of Pharmacy; Lina Cui, Ph.D., an associate professor in the department of medicinal chemistry; Todd Brushko, Ph.D., a professor in the department of pathology in the UF College of Medicine; Jonathan A. Chatzkel, M.D., a clinical assistant professor in the division of hematology & oncology in the UF College of Medicine; and Guogen Shan, Ph.D., a professor in the department of biostatistics in the UF College of Public Health and Health Professions and College of Medicine.