Glioblastoma is the most aggressive form of brain cancer, affecting mainly people of middle age. Current available therapies include surgery and radiotherapy, which is usually given in combination with chemotherapy. Despite these aggressive interventions and extensive knowledge about biology of tumor cells, glioblastoma remains incurable. Interestingly, malignant glioblastoma is highly populated by immune cells, called monocytes. These cells are recruited from the blood and enter glioblastoma in order to eradicate cancer. However, once they reach the brain tumor, monocytes change under the influence of malignant environment, and become unable to eliminate tumor cells. Instead, they support glioblastoma growth by clearing the way for cancer spread in the brain.
Dr. Gabriely’s project proposes to reprogram the monocytes and restore their intrinsic ability to destroy abnormal tumor cells. Her team will use microRNAs—recently discovered master genes—to activate monocytes. Initially, to identify potential microRNA targets, the team will compare their content between normal blood monocytes and glioma-associated monocytes. Then, therapeutic microRNAs will be identified by using a screen system of co-culturing monocytes with glioma cells. Finally, they will validate the therapeutic properties of microRNA modulation in monocytes invading glioma cells in an established mouse glioma model.
Our pioneering approach hold promise to rescue glioblastoma patients by developing a novel previously unexplored way to treat this devastating brain malignancy. Moreover, it will provide the fundamental scientific information about immune cells populating glioma for comprehensive understanding of glioma biology necessary for development of targeted treatments.