Four UAMS Researchers Receive Arkansas Breast Cancer Research 25th Anniversary Grants

By Marty Trieschmann

“Twenty-five years ago, the work of many leaders came together to form Arkansas Breast Care,” said Ronda Henry-Tillman, M.D., surgical oncologist and chief of breast oncology at UAMS. “Since then, the program has funded over 100 research grants that have undoubtedly made a powerful impact.”

Five new recipients, including four UAMS scientists, have been selected to receive grants totaling $450,000 for the 2022-23 grant year. Three of the investigators seek to better understand causes of and potential therapeutic targets for metastatic breast cancer, which accounts for most breast cancer deaths.

Martin Cannon, Ph.D. — Principal Investigator Award

Project Title: Th17-inducing dendritic cell vaccination, immune checkpoint inhibition and PARP inhibition for treatment of triple-negative breast cancer

Martin Cannon, Ph.D., professor in the Department of Microbiology and Immunology in the College of Medicine, is the recipient of the Principal Investigator Award that will provide $250,000 to support his innovative research on triple negative breast cancer (TNBC). In previous studies, Cannon found that dendritic cell (DC) vaccination increases anti-tumor immunity and improves survival following anti-PD1 therapy to boost the body’s immune response against cancer.

“DC vaccination may have potential for hard-to-treat subtypes of breast cancer, such as TNBC,” said Cannon, who is currently principal investigator of three federally funded grants — one from the National Institutes of Health and two from the U.S. Department of Defense. Cannon also leads a multi-institutional collaborative research development grant from the Ovarian Cancer Research Alliance.

“We will extend these studies to test whether clinically approved PARP inhibitors further enhance the efficacy of immunotherapy for TNBC. Successful completion of these studies will advance the translational development of immunotherapies for TNBC.”

Lisa Williams, M.S., is the research assistant on the grant and general manager of the Cannon laboratory. Richard Connor, B.S., will support the project as a research assistant.

Three UAMS researchers received $50,000 pilot awards.

Hong-yu Li, Ph.D.

Project Title: PK studies of Skp2-PROTACs

Pilot award winner, Hong-yu Li, Ph.D., will study PROTAC (Proteolysis-targeting Chimera) technology as a therapy for triple negative breast cancer. Li is a professor in the UAMS Department of Pharmaceutical Sciences in the College of Pharmacy and an experienced cancer drug researcher. He studies PROTACs, small molecule compounds with the potential to treat undruggable cancers.

Li will study the role of the Skp2 protein that has been identified as a critical player in breast cancer progression, metastasis and treatment resistance. Skp2 is overexpressed in HER2-positive breast cancer and triple negative breast cancer.

“Skp2 is a pivotal target for drug development,” said Li, who has developed novel and potent Skp2 PROTACs.

“These compounds have opened a new avenue for targeting unconventional protein interactions and led to the development of promising leads for breast cancer treatment. This translational study will help progress our basic findings into the clinical setting and will have important implications for new strategies to treat breast cancer.”

Li was involved in early studies that led to the development of the FDA approved cancer drug CDK4/6 inhibitor known commercially as Verzenio.

Horacio Gomez-Acevedo, Ph.D.

Project Title: Framework for Breast Tumor Shape and Implications for Staging and Deep Learning Segmentation of MRIs 

Horacio Gomez-Acevedo, Ph.D., an associate professor in the College of Medicine’s Department of Biomedical Informatics, will investigate cancer tumor shapes as a more refined descriptor than the usual measurements of tumor size for breast cancer staging. With co-investigators Gwendolyn Bryant-Smith, M.D., and Ronda Henry-Tillman, M.D., the end goal is to implement a framework called Elastic Shape Analysis (ESA) for the characterization of breast cancer tumors from MRIs.

“This work will allow us to compare tumors’ shape in a unified and statistically sound manner and see connections between shape with other clinical variables,” said Gomez-Acevedo.

Ultimately, this work would provide other measures of tumor shape that can potentially be relevant for tumor staging, thereby impacting cancer treatment. The study would involve three-dimensional analysis of tumor shapes, which would then be classified according to their geometric characteristics. With tumor shapes categorized and well defined, we could expand the collection with artificially generated tumors that would greatly improve deep learning models for automated identification of breast cancer from MRIs in an additional study.

Katie Ryan, Ph.D.

Project Title: Defining how Rnd3, a novel regulator of breast cancer invasion, affects the metastatic potential of breast cancer

Katie Ryan, Ph.D., assistant professor in the College of Medicine’s Department of Biochemistry and Molecular Biology, will study the role of Rnd3, a protein that has been shown in early studies by Dr. Ryan to play a role in regulating breast cancer cell invasion.

Co-investigator is Sayem Miah, Ph.D., assistant professor in the Department of Biochemistry and Molecular Biology.

“With the high incidence and poor prognosis of metastatic breast cancer, more research is needed to identify key regulators and new therapeutic targets in breast cancer metastasis,” said Ryan.

Ryan will use proteomics technology available at the state-of-the-art IDeA Proteomic Core at UAMS to better understand the underlying mechanisms in breast cancer metastasis with the purpose of identifying prognostic markers, novel therapeutic targets and treatment strategies.

A $50,000 pilot award also was awarded to Guolei Zhou, Ph.D., professor of cell biology at Arkansas State University. His study, entitled “CAP1 Mediates cAMP Signals in the Cell Type-Specific Regulation of Breast Cancer Cell Proliferation,” will investigate the Cyclase-Associated Protein 1 (CAP 1) as it regulates adhesion and proliferation in cancer cells.