Repurposing FDA-approved drugs to fight breast cancer
A potential new purpose for an old drug
“Flunarizine has been used in medical practice for decades to treat dizziness and vertigo and to prevent migraines,” Chang said. “Our study shows a new function; it also can promote degradation of cancer-promoting N-Ras.”
The researchers also tested the effect of flunarizine in a mouse model of triple negative breast cancer and found that it slowed down tumor growth. They also determined that flunarizine promotes N-Ras degradation by enhancing a natural cellular pathway called autophagy. This pathway was first discovered by the ability to provide cells a way to survive starvation by degrading and recycling cellular materials.
“Screening existing relatively safe drugs for new functions is a valuable strategy for identifying drugs that can potentially be used to treat diseases for which currently there are no available treatments,” Chang said. “Reprograming pathways that degrade cellular materials may be an effective strategy to remove a cancer driver that is otherwise hard to target.”
This study was speared by Ze-Yi Zheng, the first author on this paper. Other contributors to this work include Jing Li, Fuhai Li, Yanqiao Zhu, Kemi Cui, Stephen T. Wong and Yi-Hua Liao. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the Houston Methodist Research Institute, National Taiwan University Hospital and National Taiwan University College of Medicine in Taiwan, and the Southwest Medical University in China.
This project was supported by a P30 Cancer Center Support Grant from the National Cancer Institute (P30CA125123), the Susan G. Komen Foundation (SAC150059), the Department of Defense (W81XWH-16-1-0538), the Nancy Owen Memorial Foundation, the National Institutes of Health (R21CA185516, R21CA226567 and P50CA186784), the Cancer Prevention and Research Institute of Texas (CPRIT, RP180844) and the Ministry of Science and Technology of the Republic of China (Grant No. MOST 103-2314-B-002-067-MY3.)