Hua E. Yu, Ph.D., wants to throw a roadblock in front of melanoma cells — and a major grant from the Harry J. Lloyd Charitable Trust may help her do it.
Yu, a professor in City of Hope’s Division of Cancer Immunotherapeutics and Tumor Immunology, received a $100,000 renewable grant from the charitable trust to further her laboratory research into the signal transducer and activator of transcription 3, or STAT3, protein. STAT3 is a regulatory molecule that normally signals and directs the activity of genes; it appears to play a key role in many cancers.
“The grant from the Harry J. Lloyd Charitable Trust is a great benefit to City of Hope and my continuing work on STAT3,” Yu said. “Our laboratory research shows that inhibiting STAT3 induces direct melanoma tumor cell death, blocks melanoma angiogenesis, and activates immune responses against melanoma. The goal of our continuing studies is to translate these discoveries into clinical therapies against melanoma, and eventually other cancers.”
Grant monies will boost Yu’s drive to develop STAT3 inhibitors for melanoma cells. The effort involves a multidisciplinary team of City of Hope and outside researchers. Researchers in the divisions of Molecular Medicine and Molecular Biology and the Developmental Cancer Therapeutics program assist in a trial that tests STAT3 therapeutics and small interfering RNA (siRNA) strands that specifically block STAT3 proteins. Caltech researchers will provide nanoparticles to enable stable and tumor-targeted siRNA batches.
Researchers want to identify the most effective siRNA strand. They will then build that into a “bullet” that can infiltrate melanoma cells to block STAT3 proteins from working. Scientists will team that bullet with immune cell-based vaccines and immunotherapies and gauge whether the paired therapies boost effectiveness. Yu hopes to bring STAT3 siRNA-based therapy into clinical practice in the next three years or sooner.
Previous research showed a relationship between the STAT family of proteins and cancer development. Yu’s work established STAT3 as the specific key protein that signals the shut down of the immune response to tumors. STAT3 is tightly regulated in normal cells, but it highly active in 50 to 90 percent of human cancers. In this active state, the protein not only inhibits immune stimulating molecules, but it also produces immunosuppressive factors that further shut down the immune system.
The Harry J. Lloyd Charitable Trust, based in Overland Park, Kan., awards grants for national and international research projects into melanoma, with special consideration given to novel concepts that represent innovative lines of thinking and new investigators in the field of melanoma.