Two UF Health Cancer Center teams have been awarded pilot funding to advance innovative cancer therapeutics for Ewing sarcoma and prostate cancer.
The pilot funding was awarded to researchers in the center’s Mechanisms of Oncogenesis research program. The new projects are designed to collect preliminary data required to test novel ideas with the goal of creating a foundation for larger studies.
One project will investigate ferroptosis, a unique form of cell death potentially triggered by a cancer-causing gene, to uncover new treatment strategies in Ewing sarcoma. The other project is harnessing AI to develop specific inhibitors for a cellular pathway in prostate cancer, laying the groundwork for novel treatments to potentially improve patient outcomes.
Learn more about the research projects below.
“Ewing sarcoma’s vulnerability to ferroptosis”
Jianrong Lu, Ph.D.
Associate Professor, Department of Biochemistry and Molecular Biology
Matthew Gentry, Ph.D.
Professor and Chair, Department of Biochemistry and Molecular Biology
Ewing sarcoma is an aggressive pediatric bone cancer. The prognosis is poor for patients when the disease returns or spreads to other parts of the body. This project aims to develop new effective therapeutics for Ewing sarcoma to improve clinical outcomes.
Ewing sarcoma is predominantly driven by the EWS-FLI1 fusion gene. The researchers will test whether the fusion gene drives an iron and lipid metabolic program that makes Ewing sarcoma cells vulnerable to a form of iron-dependent cell death called ferroptosis.
The team will characterize the metabolic and pro-ferroptosis phenotype of Ewing sarcoma. Using preclinical models, they will also explore ferroptosis-inducing compounds to target the disease. The team aims to uncover a novel druggable target of Ewing sarcoma, which could translate into new treatment strategies.
The project will also evaluate the effectiveness of compounds that induce ferroptosis in the treatment of Ewing sarcoma. These inducers could be promising therapeutics that may effectively target Ewing sarcoma.
“HIRA/H3.3 pathway inhibitors for castration-resistant prostate cancer treatment”
Alexander Ishov, Ph.D.
Associate Professor, Department of Physiology and Aging
David Ostrov, Ph.D.
Associate Professor, Department of Pathology, Immunology and Laboratory Medicine
Viacheslav Morozov, Ph.D.
Assistant Scientist, Department of Physiology and Aging
Prostate cancer is the second leading cause of cancer mortality in men in the United States. When the disease returns after treatment with androgen deprivation therapies, it’s called castration-resistant prostate cancer. Castration-resistant prostate cancer is the cause of almost all prostate cancer-related deaths and is often characterized by disease spread to other parts of the body.
To date, treatment options for castration-resistant prostate cancer are scarce and include chemotherapy drugs called taxanes. Clinical use of taxanes is limited because patients acquire resistance to the drugs, making it vital to identify new druggable targets.
The new project is based on the team’s findings indicating the HIRA/H3.3 pathway has a critical function in metastatic castration-resistant prostate cancer. The research team will develop small-molecule inhibitors for this pathway with the hope of identifying new therapeutic options for patients.
Researchers will use UF’s supercomputer, the HiPerGator, to select candidate compounds. AI-generated structures of the proteins involved in the pathway will be the basis for structure-based screening using HiPerGator. The most promising compounds will be optimized for better performance and tested in preclinical mouse models to determine their bioavailability, toxicity and efficacy.
The team is uniquely positioned to address these questions and includes expertise in HIRA/H3.3 biology in prostate cancer and structural biology and drug discovery. HIRA/H3.3 is involved in several types of cancer, including brain, pancreas and breast, and the research is expected to move these fields forward.
The UF Health Cancer Center’s pilot funding programs receive crucial support from the state of Florida through the Casey DeSantis Cancer Research Act (Fla. Stat. § 381.915).
