Abstract 68: Precision medicine in glioblastoma: cortical network disruptions, biomarker development, and multimodal therapeutic strategies

Abstract Glioblastoma (GBM) is a highly aggressive brain tumor characterized by diffuse infiltration into surrounding brain tissue, disruption of neural circuitry, and interactions among neurons, astrocytes, and blood vessels. This infiltration leads to severe functional impairments, including neuronal hyperexcitability, cognitive deficits, and in some cases seizures. While substantial progress has been made in understanding GBM’s molecular mechanisms, less is known about how tumor progression alters brain connectivity, neural oscillations, and behavior. Using advanced transgenic mouse models (e.g., GCaMP6s, GCaMP6f, jGCaMP8m, and Vgat-Cre-ChR2) and custom-built optical microscopes, we performed large-scale, high-speed neural recordings and manipulations across over 10 million neurons spanning 60 brain regions in vivo in pre-clinical GBM models. Our approach integrates deep learning tools for multimodal analysis of brain activity, pupil dynamics, and orofacial behaviors, supported by computational models optimized with quantum computing. Preliminary data reveals significant tumor-induced disruptions in neural and behavioral dynamics. Tumor growth in the mouse striatum is associated with increased pupil size, restricted gaze range, and reduced interhemispheric connectivity. Furthermore, oscillatory activity shows a striking shift, with decreases in delta power accompanied by increases in theta and alpha band power. These findings highlight GBM’s capacity to disrupt normal neural rhythms and connectivity. Our work underscores the potential of using behavioral relevant parameters as a non-invasive biomarker for early detection of GBM-induced neural dysfunction. Future studies will focus on leveraging these insights to develop novel therapeutic strategies targeting tumor-induced disruptions in oscillatory activity. By integrating cutting-edge imaging technologies and computational methods, our findings have significant implications for improving early diagnosis and treatment outcomes for GBM patients. Citation Format: Tenesha Connor, Frederick Bell, Macit Emre Lacin, Miguel Maldonado, Kemal Ozdemirli, Anthony Sloan, Justin Lathia, Murat Yildirim. Precision medicine in glioblastoma: cortical network disruptions, biomarker development, and multimodal therapeutic strategies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 68.