Project 461900

Glioblastoma (GB) is the most malignant primary brain tumor in adults. The present standard of care includes maximal surgical removal of the tumors followed by treatment with Temozolomide (TMZ) and ionizing radiation (IR). Despite these intense efforts, the median survival rate for GB patients remains less than ~18 months following diagnosis. Multiple mechanisms may underlie the resistance of GB to therapy. Brain tumor stem cells (BTSCs) are a rare population of self-renewing stem cells in GB tumors that are highly proliferative. At the same time, they also have the capacity to give rise to all the cellular subpopulation within a tumor. BTSCs play important roles in GB resistance to therapy and tumor relapse. We have discovered that two molecules, LGALS1 and HOXA5 function on the same pathway to control BTSCs and glioblastoma resistance to IR. In this proposal, we will investigate how LGALS1/HOXA5 signalling pathway regulates BTSCs and glioblastoma tumors. Importantly, we will determine the mechanism of action of drugs that can suppress LGALS1/HOXA5 axis. This work will generate important knowledge for better understanding and treatment of GB.