$8.9M grant funds research on treatment for one of deadliest cancers

The Hollings Cancer Center has received an $8.9 million grant from the National Cancer Institute to foster collaboration across clinical and laboratory research for the study of signaling in sphingolipids, a class of lipids involved in the growth of solid tumor cancers.

The grant funds three projects, including a Phase II clinical trial of a new therapy to treat advanced hepatocellular carcinoma, the most common primary malignant cancer of the liver and one of the deadliest cancers. Currently, there is only one approved therapy for the condition. The five-year survival rate for patients with liver cancer is 17 percent.

The grant will bring together more than 20 scientists at Hollings Cancer Center to make clear the roles of lipid signaling mechanisms thought to regulate cancer cell proliferation, resistance to cell death and metastasis in solid tumors. The Hollings-based team will develop new therapeutic strategies not only aimed at liver cancer but also other tumors, including prostate, bladder and kidney cancers.

Besim Ogretmen, Ph.D., is the endowed chair in lipidomics and drug discovery in the SmartState Center for Lipidomics, Pathobiology and Therapy and a professor of biochemistry and molecular biology at MUSC. He 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,” Ogretmen said. “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 studying how lipid signaling is involved in tumor metastasis in solid tumor cancers. He hopes to learn more about how to keep cancer from spreading to other parts of the body and identify biomarkers to detect disease earlier.

A second project will study how cancer cells become resistant to radiation therapy. It’s designed to find ways to improve patients’ response to radiation and chemotherapy. This study, led by Christina Voelkel-Johnson, Ph.D., and James Norris, Ph.D., will primarily focus on prostate cancer, but may also apply to all solid tumors.

Carolyn D. Britten, M.D., chief of the Division of Hematology and Oncology in the Department of Medicine and associate director for clinical investigations at Hollings Cancer Center, will act as principal investigator for the Phase II clinical trial that’s part of the third project. The Phase II trial, expected to begin at MUSC this summer, is intended to evaluate the effectiveness and safety of YELIVA as a second-line monotherapy in people with advanced hepatocellular carcinoma. YELIVA is a sphingosine kinase-2 (SK2) selective inhibitor.

The study will enroll patients whose tumors have grown after being treated with sorafenib (Nexavar). The new SK2 selective inhibitor was developed by Charles Smith, Ph.D., while he was at MUSC. It was 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 some funding for this part of the project.

As principal investigator for the overall grant, Ogretmen brings experience as an internationally renowned investigator with a strong 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. 

Philip Howe, Ph.D., professor and chairman of the MUSC Department of Biochemistry and Molecular Biology, said Ogretmen’s work is distinctive. “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,” Howe said. “His leadership on this multi-project program is a reflection of this strength and focus, representing a blend of basic and translational research.”

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Preliminary data leading to the success of this award was supported in part by the NIH-NCATS Clinical and Translational Science Award (CTSA) program through the South Carolina Clinical & Translational Research Institute (Grant Numbers: UL1TR000062 and UL1TR001450); NIH-NIGMS COBRE in Lipidomics and Pathobiology (Grant Number: P30GM103339); and multiple shared resources (Biostatistics, Lipidomics) supported by the NIH-NCI Cancer Center Support Grant (Grant Number: P30 CA138313).