Striking brain tumor metabolic vulnerabilities through identification of synthetic lethal pairs

The heterogeneity in patient-specific drug response could be the major obstacle for this proposal, however, by i) increasing the number and the diversity of PDO enrolled in this project, and ii) strictly controlling the experimental culture conditions, the patient genetic background will be excluded from the proposed synthetic lethality screening with the scope to focus only on common metabolic vulnerabilities driven by the hypoxic and acidic tumor microenvironment. For this reason, the implementation of our cell line library with the CBTN resources will tremendously improve the significance of our findings, thus accelerating the translational impact of this project. Six different PD-BT derived in our lab are available for this project, together with Med-411, Med-2112, Med-114, EPD-710FH, ATRT-310FHTC, ATRT-311FHTC, GBM-511FHTC, all purchased from the Olson Lab at the Fred Hutchinson Cancer Research Center.