UTHSC researchers working to find new treatments to combat breast cancer metastasis recently pulled in a major national award. Wei Li, PhD, distinguished professor of Pharmaceutical Sciences and director of the Drug Discovery Center in the College of Pharmacy, and Tiffany Seagroves, PhD, professor of Pathology in the College of Medicine, are principal investigators on a $3.07 million grant from the National Cancer Institute for a project to develop a new series of drugs targeting microtubules to stop the spread of breast cancer to the brain and bone. Duane Miller, PhD, professor emeritus, and Zhongzhi Wu, PhD, assistant professor, both in the Department of Pharmaceutical Sciences in the College of Pharmacy, are co-investigators.
A major clinical challenge in breast cancer care is treating metastatic disease, particularly brain and bone metastases. Mainline therapies, including conventional chemotherapeutic drugs targeting microtubules such as taxanes, have low brain penetration, often are subject to drug resistance, and have long-term side-effects, such as neurotoxicity.
Dr. Li and Dr. Miller have been working together for over 10 years to develop a new generation of tubulin inhibitors for various cancer types. Their efforts led to an investigational new drug, sabizabulin, which suppresses primary tumor growth and metastasis in several types of tumor models and is effective in overcoming taxane resistance. Over the past five years, Dr. Li and Dr. Miller collaborated with Dr. Seagroves to evaluate these tubulin inhibitors for late-stage breast cancer. In their recent studies, the team found that modified sabizabulin analogs have high brain penetrability and excellent efficacy in multiple taxane-resistant tumor models.
The goals of this new project are to structurally optimize this class of analogs for potency and the ability to penetrate the brain, and to create novel analog drug conjugates (made by joining a cancer drug molecule to another molecule that preferentially interacts with a specific type of cell in the body). For treating bone metastases, Drs. Li and Seagroves will conjugate new sabizabulin analogs with bisphosphonates, a drug class used to increase bone strength. They will test the optimal conjugate by comparing it to a reference chemotherapy in animals with bone-destroying breast cancer.
“The addition of a new generation of tubulin inhibitor to the existing panel of chemotherapeutic drugs could help to improve metastatic breast cancer patient overall survival and quality of life,” Dr. Li said. “In addition, patients diagnosed with other types of metastatic solid tumors in which tubulin inhibitors are currently standard of care could also benefit.”