Core Summary The overall goal of this SPORE application is to develop more effective targeted molecular therapies and biomarkers for gliomas. The three proposed projects of the SPORE focus on 1) improving BRAF therapeutics for BRAF-mutant pediatric gliomas; 2) therapeutic targeting of metabolic vulnerabilities in diffuse midline gliomas 3) novel approaches to combating resistance to IDH inhibitors in IDH-mutant gliomas. The Pathology Core will support the goals of these SPORE Projects through three aims. Aim 1 involves providing professional biorepository services so that projects have access to essential adult and pediatric human glioma tissues, organoids/neurospheres, cell lines, and xenografts with matching clinical and pathological data from patient whose tumors have appropriate drug targets and phenotypes of interest to the project aims. The Core will also support project clinical trials through dedicated Core pathologist and clinical research coordinator who will perform tumor sample collection, processing, characterization, and distribution. In Aim 2 the Core will serve as a centralized resource for project-relevant patient-derived organoids/neurospheres, cell lines and xenografts of gliomas including rare BRAF, H3F3A, and IDH mutant models by creating and authenticating models. For Aim 3 the Core will develop and apply innovative expertise and technologies to support project aims and clinical trials. These areas include integration of multimodal imaging techniques in patient samples including mass spectrometry imaging of drug distribution within tissue sections, digital pathology support with deep learning approaches, and pathology collaboration to generate and interpret spatial profiling data. By centralizing each of these activities, the Pathology Core will ensure the reproducibility of data and effective use of finite glioma tissue resources essential to the collaborative translational research projects of the SPORE program.