The Medical University of South Carolina's (MUSC) Hollings Cancer Center received an $8.9 million grant from the National Cancer Institute designed to foster collaboration across clinical and laboratory research for the study of signaling in sphingolipids, a class of lipids known to be involved in the growth of solid tumor cancers.
The grant includes three projects, including a Phase II clinical trial of a new therapy for the treatment of advanced hepatocellular carcinoma (HCC), the most common primary malignant cancer of the liver and one that experiences one of the highest mortality rates among cancers. Currently, there is only one approved therapy for HCC. The five-year survival rate for patients with liver cancer is 17 percent.
The program project grant will bring together over 20 cancer scientists at the Hollings Cancer Center with a goal of elucidating the explicit roles of lipid signaling mechanisms which are thought to regulate cancer cell proliferation, resistance to apoptosis (cell death), and metastasis in solid tumors (when cancer spreads from its primary site to other parts of the body). Utilizing mechanistic information gained from these studies, the Hollings-based scientific team will develop new therapeutic strategies not only targeted for liver cancer but with applicability to other solid tumors, such as prostate and urinary (bladder/kidney) cancers.
Besim Ogretmen, Ph.D., Endowed Chair in Lipidomics & Drug Discovery in the SmartState® Center for Lipidomics, Pathobiology and Therapy and professor of Biochemistry & Molecular Biology at MUSC, will oversee the program as principal investigator.
"We are excited about the opportunities in this large, team-based program to share information from laboratory research over into clinical applications, and then take information learned from the clinical applications back into the lab," said Ogretmen. "Through a collaborative effort, our goal is to provide cancer patients the very best care based on the latest cutting-edge research."
In addition to his role as principal investigator, Ogretmen will lead a project designed to study how lipid signaling is involved in tumor metastasis in solid tumor cancers, increasing knowledge regarding inhibiting tumor metastasis and working to identify biomarkers to detect disease earlier.
A second project area will study how cancer cells become resistant to radiation therapy, working to improve response to radiation and chemotherapy. This study, led by co-project leaders Christina Voelkel-Johnson, Ph.D., and James Norris, Ph.D., will primarily focus on prostate cancer, but will have applicability to all solid tumors.
Carolyn D. Britten, M.D., chief of the Division of Hematology/Oncology in the Department of Medicine at MUSC and Associate Director for Clinical Investigations at the MUSC Hollings Cancer Center, will act as principal investigator for the Phase II clinical trial embedded in the third project. The Phase II trial, expected to commence at MUSC in the third quarter of 2016, is intended to evaluate the efficacy and safety of YELIVA™ (ABC294640) as a second-line monotherapy in patients with advanced HCC. YELIVA™ is a proprietary, first-in-class, orally-administered sphingosine kinase-2 (SK2) selective inhibitor. The study will enroll patients who have experienced tumor progression following treatment with first-line single-agent sorafenib (Nexavar®). The SK2 selective inhibitor was developed by Charles Smith, Ph.D., while at MUSC and later sold to RedHill Biopharma. Smith is currently on faculty at Penn State University and will be a co-principal investigator on this trial. RedHill Biopharma will provide additional funding for this area of the project.
As the principal investigator for this overall grant, Ogretmen brings experience as an internationally renowned investigator with a strong scientific track record in the field of lipid signaling and cancer. He has made significant contributions to the fields of cancer and aging biology at a mechanistic level through his pioneering work on the regulation of telomerase by the bioactive sphingolipid ceramide.
"Dr. Ogretmen's work is distinct in that he not only focuses on basic molecular mechanisms but also demonstrates the significance of his findings in human diseases with a keen interest toward therapeutic development. His leadership on this multi-project program is a reflection of this strength and focus, representing a blend of basic and translational research," commented Philip H. Howe, Ph.D., professor and chair, MUSC Department of Biochemistry & Molecular Biology, Hans & Helen Koebig Chair in Oncology.
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