Elucidation and Small Molecule Inhibition of Slug-induced Invasion and Metastases in Glioblastoma and Other Cancers

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Dr. Mark Johnson is an established member of the Department of Neurosurgery at Brigham & Women’s Hospital and an expert on brain tumors. He has already accomplished several highly original investigations into the causes of glioblastoma. In this grant he is studying “transcription factors”—signaling proteins within the cell that turn both genes and proteins on and off and contribute to cancer growth. Specifically, Dr. Johnson has identified the cell regulator SNAI2/Slug (called “slug” by people in the field) that is highly expressed in glioblastomas and has strong circumstantial evidence of participation in continued growth of the tumor.

One exciting element related to this project is that slug-induced invasion can be inhibited by small molecule inhibitors, some of which are currently in clinical trials for other applications. This is an entirely new strategy to decrease the invasion of glioblastoma to adjacent parts of the brain and is likely to have implications for other tumors and metastases.

Dr. Johnson’s work will be done with mouse models of glioblastoma, metastatic melanoma, and metastatic breast cancer. In addition, the proposal will study the way in which glioblastoma cells migrate in a special laboratory dish, observing the effects of the small molecule inhibitors on this migration.

This is focused work on the pathways of brain tumor development never investigated before and has the potential to be developed into a new series of drugs for brain tumors.