Uncovering the signaling mechanisms allowing medulloblastoma progenitor cells to orchestrate tumor relapse
Medulloblastoma is the most common brain tumor in children. Despite the use of very aggressive treatments, 30% of these tumors will eventually grow back. Recurrent medulloblastoma is normally metastatic, and extremely hard to treat. Sadly, survival for children whose tumors recur is less than 10 months. It is, therefore, very important to find treatments that not only stop the growth of the tumors, but also prevent their reappearance. A series of experiments allowed us to find subsets of partially differentiated tumor cells resembling healthy astrocytes and oligodendrocytes in the brain. We have seen that these cells, likely due to their dormant state and distinct profile, have the ability to evade therapeutics targeting proliferative cells, and to grow new tumors. We believe that future therapeutic approaches should combine drugs blocking tumor growth, with those specifically eliminating this subset of therapy-resistant cells. Our project is aimed at designing game-changing combination therapies that will ensure a tumor free future for children with medulloblastoma.
Thirty percent of children with medulloblastoma will relapse and succumb to their disease. Due to its severity, novel therapeutics aimed at preventing tumor recurrence are urgently needed. Our data suggests that medulloblastoma relapse is facilitated by treatment-resistant cells that share similarities with normal astrocytes and oligodendrocytes in the brain. Here, we propose to uncover the mechanisms that these cells use to evade therapies and grow new tumors, as well as drugs with the ability to eliminate them. The purpose of this project is to develop combination therapies aimed at not only blocking the growth of medulloblastoma tumors, but at preventing them from growing back in the future. The ultimate goal of our research is to test the efficacy of these novel combination therapies in clinical trials, for which we have included in our proposal a translational team of collaborators.
