Targeting the Surface-ome of Embryonal Brain Tumors
Collaborators
Stéphanie Puget, MD, Necker Hospital
Siddhartha S. Mitra, PhD, University of Colorado Denver
Project Summary: Deregulations in biological networks are key events in the pathogenesis of cancer and an understanding of these events should open the road to improved therapeutic strategies. In this context, molecules (including proteins, glycoproteins, etc.) located at the surface of the tumor cells (surface-ome) are appealing candidates to target tumor cells as they are easily accessible and often specific to the tumor. However, the characterization of these molecules has been a real challenge. Here, we propose to establish the workflow to decipher the landscape of proteins present at the surface of tumor cells. In order to tackle this key question, as proof of principle, we will investigate the surface-ome of one of the most common malignant pediatric brain tumors, medulloblastoma. We will work in concert with the proteomic platform at the Institut Curie to develop the proposed approach. Since we have a direct access to primary medulloblastoma samples (Patient Derived Xenografts and fresh tissues from surgery) through our collaboration with Pr. Stéphanie Puget, pediatric neurosurgeon (Necker, France), we will be able to test immediately our protocols on fresh samples. Together, we are in the unique position to (i) develop a workflow aiming first at characterizing the proteome at the surface of medulloblastoma cells, (ii) translate this workflow to any type of pediatric tumors, and (iii) develop further strategies targeting the surface-ome of pediatric tumors. Together, we anticipate that within these 12 months, the pilot funding will allow us to establish the basis of a future RFA.
Project Update 2020: During the last 12 months, and thanks to the Pilot funding from ALSF we were able to establish the workflow to decipher the landscape of proteins present at the surface of medulloblastoma tumor cells using mass spectrometry (Collaboration with Dr. Loew, Institut Curie). Overall, we anticipate that besides the characterization of the medulloblastoma landscape, we will be able to (i) apply this workflow to any type of pediatric tumors, (ii) develop further strategies targeting the surface-ome of pediatric tumors and (iii) translate our findings towards the discovery of new biomarkers and targets for novel therapeutic avenues in the field.
