A researcher exploring new anticancer drugs for triple-negative breast cancer has been named the 2020 Vera Bradley Foundation Scholar. Ryan Higgins, PhD, a postdoctoral researcher in the laboratory of Chunhai “Charlie” Hao, MD, PhD, is the new scholar. From Madison, Ind., Higgins is the first Vera Bradley Scholar from the Hoosier state.
The Vera Bradley Foundation Scholars Career Development Program provides two years of research funding to a postdoctoral fellow to pursue a breast cancer research project. As the 2020 Vera Bradley Foundation Scholar, Higgins’ research project is “Development of SUMO1 Degraders as the First-in-class Drugs for Metastatic Breast Carcinoma.”
A first-in-class drug means that the therapeutic would use a new, innovative mechanism to treat the cancer; this is the first such project for researchers at the Vera Bradley Foundation Center for Breast Cancer Research.
“Triple negative breast cancer is termed that because it lacks hormone receptors that other breast cancers possess, therefore, you can’t target those receptors therapeutically like other cancers,” Higgins said. “Because of the lack of receptors to target, the development of triple negative breast cancer therapeutics has been a challenge.”
Instead, Higgins will work alongside Hao to target a protein called SUMO1 (small ubiquitin-related modifier 1). Hao’s research team had previously identified the first small molecule degraders of SUMO1 protein, which has been implicated in driving breast cancer as well as many other cancers.
Hao is co-program leader of the Experimental and Developmental Therapeutics research program at the at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center and a member of the Vera Bradley Foundation Center for Breast Cancer Research at IU School of Medicine.
“Traditional therapeutics have focused on inhibiting proteins that drive cancer,” Higgins said. “Although inhibitors are proven effective therapies, drug resistance is often an unavoidable problem, therefore novel therapies are needed. Within the past five to 10 years, a new class of therapeutics called protein degraders have emerged. They work by degrading, rather than inhibiting, a protein of interest from the cell, potentially making them a more effective therapeutic than inhibitors.”
Higgins is working now to develop a drug that functions as a SUMO1 protein degrader.
“We have performed several drug screens and identified a compound that degrades the SUMO1 protein, and we have found that it’s very effective in treating breast cancer cell lines, specifically triple negative breast cancer cell lines,” Higgins said.
Researchers have also shown that the compound they are developing effectively slows tumor growth in patient-derived xenografts, or mouse models developed with patient tumor cells.
“We have modified the compound through medicinal chemistry to make it more specific to its target. This lowers toxicity and increases its ability to degrade the SUMO1 protein, which in turn kills the cancer cells while limiting affects to normal cells,” Higgins said.
Ultimately, Higgins hopes his research will result in clinical applications for breast cancer patients.
“I’m honored to be named this year’s Vera Bradley Scholar. I look forward to working diligently on the research proposal and trying to bring this research to a clinical trial at IU,” he said.
Higgins earned a bachelor’s degree in biochemistry from Indiana University Southeast and a doctoral degree from Florida State University. He joined Hao’s lab in 2019. In addition to Hao, mentors for Higgins’ project are Harikrishna Nakshatri, BVSc, PhD, and Kathy D. Miller, MD.
