From Progressnotes: MUSC Health Year in Review

World-Class Team Collaborates To Develop a New Class Of Cancer Therapeutics

Precision therapies target specific mutations to knock out pathways involved in cancer development. Cancer is devious, however, and can develop resistance to these therapies by using redundant pathways. Zihai Li, M.D., Ph.D., Chair of the Department of Microbiology and Immunology, has shown that the heat shock protein grp94 is a master regulator of many oncogenic pathways, making it an attractive drug target. A grp94 inhibitor could block multiple cancer-associated pathways at once, reducing the likelihood of resistance.

In September 2015, MUSC Hollings Cancer Center and its partners Memorial Sloan Kettering and the University at Buffalo were awarded a five-year $6.8 million program project grant from the National Institutes of Health to elucidate the underlying biology and structure of the heat shock protein grp94 and to develop grp94 inhibitors for clinical trial. The award will fund three projects and two cores to accelerate the development of grp94-based cancer therapeutics.

Li is the national principal investigator for the grant, will head up its administrative core, and will lead a project to use genetic, biochemical, and immunological tools to elucidate the mechanisms by which grp94 promotes cancer and to assess the therapeutic potential of grp94 inhibitors against triple-negative breast cancer.

Gabriela Chiosis, Ph.D., of Memorial Sloan Kettering, whose laboratory has previously developed successful inhibitors against other heat shock proteins, will head the Medicinal Chemistry core and develop identified grp94-inhibiting compounds into pharmacologically viable agents for clinical trial. Structural biologist Daniel T. Gewirt, Ph.D. of the University at Buffalo will map the atomic structure of grp94 so that new inhibitors can be identified and engineered for better selectivity and binding capacity.