The overall goal of this SPORE application is to develop more effective targeted molecular therapies and biomarkers for glioblastoma. The four proposed projects of the SPORE focus on 1) targeted therapeutics to treat BRAF-mutant pediatric gliomas; 2) development of improved targeted therapies for IDH-mutant gliomas; 3) combining targeted CDK4/6 inhibitors with immunotherapies to treat glioblastoma; and 4) evaluation of Nlgn3 as a novel therapeutic target in gliomas. The Pathology Core will support the goals of these SPORE Projects by providing expert neuropathologic review, specimen banking, genomic analysis and clinical trial support. In addition, the Pathology Core will be a centralized resource for validated patient derived cell lines and xenografts of gliomas. The Core will also offer innovative CyTOF on a slide multiplex imaging (MIBI), mass spectrometry imaging of drug distribution within tissue sections, and liquid biopsy of circulating tumor cells (CTC) to determine responses to targeted therapies in clinical trials. By centralizing 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 of the SPORE program.