Abstract Background: Germline, pathogenic mutations in BRCA2 (BRCA2mut) are the strongest genetic risk factor for pancreatic cancer in men and women; pathogenic variants in this gene are implicated in about 5% of men and women with heritable risks of this cancer type. Moreover, BRCA2mut are associated with increased risk of pancreatic cancer inHispanic/Latino populations specifically. Patient-specific induced pluripotent stem cell (iPSC) methods create opportunities to modelhuman diseases in vitro. iPSCs derived from patients with known genetic mutations carry thepatient's unique genetic background, to provide platforms for studying the functional effects ofspecific genes. Several inherited disease models created from iPSCs have successfully replicated high-risk cancers. This study aimed to utilize iPSC-based modeling to investigate thefunctional impact of pathogenic BRCA2mut on early-stage pancreatic tissues (PT) and genomicalterations that contribute to pancreatic cancer (PC) progression. Methods: We generated iPSC from BRCA2mut positive and BRCA widtype (BRCAWT) women and men. From these BRCA2mut and BRCAWT iPSCs we generated organoid models of pancreatic ductal and acinar precursors. In addition, we used lentiviral targeting to mimic thefunctional effects of specific genes involved in early stage pancreatic cancer pathogenesis, specifically TP53 knockdown (using a TP53 siRNA), and TP53 and/or KRAS overexpression (TP53 R175H and R273H; KRAS G12V) respectively. Results: Following differentiation into PT organoids heterozygous for BRCA2mut pancreatic ductal cells show specific cellular abnormalities - neoplastic transformation, ductal formation, expression of cancer-specific biomarkers - compared to BRCAWT controls suggesting that BRCA2 haploinsufficiency contributes to the observed phenotype. PC models from BRCA2mut subjects exhibit abnormalities reminiscent of early-stage neoplastic development. Importantly, PC organoids with combinations of BRCA2mut, TP53 and KRAS alterations exhibited a moreaggressive PC phenotypes compared to BRCA2mut and BRCAWT organoids alone, and sharedgenomic signatures with primary PCs. Conclusion and Impact: iPSC-derived organoids can accurately replicate BRCA2mut andBRCAWT pancreatic precursor tissues. This allows cancer to evolve in a dish, making it an ideal model for mechanistic studies and screening approaches to identify novel drug targets. Citation Format: Yi Xu, Nur Yucer, Alyssa Okimoto, Bobbie J. Rimel, Kate Lawrenson, Pei Wang, Simon A. Gayther. Pancreatic cancer modeling in germline BRCA2 mutation carriers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 353.

Abstract Introduction: Replication repair deficiency (RRD) is a pan-cancer mechanism caused by germline and/or somatically acquired mutations in the replication repair machinery - DNA polymerase proofreading and the mismatch repair (MMR) system. Germline monoallelic (Lynch Syndrome, LS) or biallelic (Constitutional Mismatch Repair Deficiency, CMMRD) mutations in MMR genes are present in 5-10% of glioblastomas in children, adolescents, and young adults. RRD gliomas are lethal, chemoradiation-resistant cancers, characterized by universal hypermutation and variable susceptibility to immune-checkpoint inhibition (ICI). These tumors exhibit variability in patient age of onset, type, location, and response to ICI. Methods: To understand the clinical and biological differences associated with RRD central nervous system (CNS) tumors, we used germline mutations and brain development-specific Cre-drivers to generate murine models that recapitulate the phenotypic and genomic characteristics of each human RRD subgroup: 1) MMRD+PPD (Nestin- and Olig2-Cre+/ Msh2LoxP/LoxP/PoleS459F/+ and LSL-PoleP286R/+): MMR-deficiency (MMRD) in combination with polymerase proofreading deficiency (PPD). 2) MMRD-only (Nestin-Cre+/Trp53LoxP/LoxP and Msh2LoxP/LoxP or Mlh1-/-): MMRD lacking PPD associated with TP53 mutations. Results: Using trans-species comparative approach, we elucidated a mechanistic model of RRD-driven brain tumorigenesis. We revealed that the cell-of-origin significantly contributes to determining brain tumor type, location, and age of tumor onset, suggesting a strong impact of early- or late-RRD mutational onset in shaping tumor biology (p<0.0001). Importantly, using murine neural stem cells, we discovered that germline mutagenesis onset directly influences timeline of brain tumor formation and survival between CMMRD and LS patients (p<0.05). We further demonstrate the interplay between POLE mutations and MMRD status in modulating the likelihood of brain tumorigenesis in both species. To understand the interaction between hypermutation and the immune system, we characterized the tumor immune microenvironment in spontaneously forming tumors. We uncovered subgroup-specific immune landscapes, with CD8+ T cell activity emerging as a key modulator in controlling brain tumor growth (p<0.0001), suggesting an underlying mechanism that may inform therapeutic strategies in RRD patients. Significance: Altogether, our models accurately mimic the human condition, providing a mechanistic framework of RRD-driven brain tumorigenesis, optimization of subgroup-tailored immunotherapy approaches, and putative surveillance protocols. Citation Format: Zoya Aamir, Melissa A. Galati, Emma Gattoni, Owen Crump, Nemanja Ilic, Anirban Das, Nicholas R. Fernandez, Angel K. Wong, Lucie Stengs, Jose R. Dimayacyac, Yuan Chang, Vanessa Bianchi, Melissa Edwards, David Malkin, Cynthia Hawkins, Nuno M. Nunes, Uri Tabori. Trans-species analysis of central nervous system developmental-specific replication repair deficiency reveals differential patterns of gliomagenesis and response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 631.

Abstract Purpose: Glioblastoma (GBM) exhibits functional heterogeneity and therapeutic resistance across disease stages. We developed a 3D magnetic spheroid platform to assess invasion, stem cell plasticity, and therapeutic response in newly diagnosed and recurrent patient-derived gliomaspheres under physiologically relevant hypoxic conditions. Methods: Gliomasphere migration was monitored by live-cell imaging under hypoxia. Stem cell plasticity was assessed by CD44 expression using laser scanning confocal microscopy, while basal MCL-1 levels and CDK inhibitor targets were analysed by Western blotting. Cell viability and apoptosis were evaluated using WST-1 and Caspase-3/7 Glo assays. Invasion dynamics in response to Temozolomide (TMZ) and novel CKIs (CYC065 & THZ1) were assessed across disease stages. Results: Newly diagnosed gliomaspheres exhibited dynamic CD44 plasticity, whereas recurrent gliomaspheres maintained stable CD44 expression. In unmatched samples, newly diagnosed tumors were more invasive than recurrent tumors; this difference was not observed in patient-matched pairs. Across all stages and oxygen conditions, CDK inhibitors far more effectively suppressed invasion and induced apoptosis than TMZ, independent of CD44 status. CKI activity was associated with MCL-1 downregulation and inhibition of CDK2/7/9, and was maintained despite fluctuations in BCL-2 family proteins under hypoxia, confirmed by reduced viability and increased Caspase-3/7 activity. Conclusions: This 3D magnetic spheroid platform captures spatially resolved functional heterogeneity in glioblastoma and enables precise evaluation of invasion and therapeutic response. Novel CDK inhibitors robustly suppress invasion and induce apoptosis across disease stages and oxygen conditions, highlighting their potential as broadly effective therapeutics. This work demonstrates how spatial 3D modeling can uncover hypoxia driven plasticity and inform translational strategies in glioblastoma. Generative artificial intelligence was used to assist with language editing and clarity of the abstract; all scientific content and conclusions were determined by the authors. Citation Format: Niamh M. Scully, Brenton L. Cavanagh, Heiko Duessmann, Jochen H.M. Prehn, Brona M. Murphy. 3D magnetic gliomasphere modeling reveals CDK inhibitor mediated suppression of migration in newly diagnosed and recurrent glioblastoma under hypoxic conditions [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr B029.

Abstract Tumor heterogeneity fueled by plasticity and genetic diversification of cancer cells is key to therapy failure of malignant glioma. We implemented spatial and genetic platforms at single cell resolution to explore the trajectory of evolution of glioblastoma. Using spatial analysis of whole glioblastoma sections, we established a homotypic clustered cell identity paradigm whereby tumor cell state coherence was maximal in cells organized in homotypic clusters, whereas dispersed cells downregulated the original state, acquired alternative phenotypes and exhibited changes in the microenvironment, thus linking the process of plasticity to loss of the cell adhesion mechanisms that preserve the clustered spatial pattern of glioblastoma cells. We also used single cell DNA-sequencing methods integrated with the single cell transcriptome of patient-matched primary-recurrent glioblastoma pairs to resolve the clonal substructure of untreated glioblastoma and determine the clonal evolution at recurrence driven by therapeutic resistance. The evolutionary trajectory of glioblastoma identified a bottleneck model as the predominant pattern of evolution and converged on the identification of a rare persister subclonal state in primary glioblastoma exhibiting distinct phenotypic hallmarks that evolves and diversifies to populate the recurrent tumor mass. We used preclinical tumor models to trace the individual lineages associated with the persister subclones and experimentally illuminated the biological and metabolic activities of the persister cellular state in brain tumors. Persister glioblastoma cells in untreated tumors lacked spatial segregation and were independent predictors of timing to recurrence for glioblastoma patients. Thus, genetic and non-genetic co-evolution mechanisms forge the acquisition of plasticity and therapy resistance in glioblastoma. Citation Format: Antonio Iavarone. Shaping tumor cell plasticity and therapy resistance in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr IA005.

Abstract Background: Central nervous system (CNS) border pathways, including meningeal lymphatics, trigeminal neurovascular networks, and cribriform plate conduits, are increasingly recognized as routes for immune surveillance and therapeutic access to the brain. However, strategies to actively enhance trafficking through these interfaces remain limited, particularly for nanotherapeutic delivery in glioblastoma (GBM). Here, we developed facial dermal based system to deliver immune-modulating nanoparticles through the neuro-lymphatic network. Methods: To overcome physical barriers limiting immunotherapeutic access to CNS and peripheral immune sites, we implemented two mechanistically integrated strategies. First, we established facial intradermal (i.d.) delivery combined with iontophoresis as a minimally invasive approach to enhance CNS trafficking across the brain border interfaces. Iontophoresis utilizes low-intensity electric fields to promote directional transport of charged therapeutics into deeper tissues. Second, we engineered charged nanotherapeutic particles bimodal Spherical Nucleic Acid (bi-SNA) platform designed to leverage electric field-guided transport from the face to the CNS borders while activating cGAS–STING and inhibiting STAT3. This bi-SNA consists of a 15-nm gold core functionalized with a hairpin oligonucleotide containing an unpaired G5 repeat loop flanked by STAT3-decoy palindromic sequences, enabling simultaneous cGAS activation and cytosolic sequestration of STAT3. Results: Iontophoresis-augmented i.d. delivery achieved significantly enhanced nanoparticle trafficking across CNS border pathways compared with i.d administration. IVIS/CT imaging of fluorescent probe-tagged SNA in mouse whole-head demonstrated robust SNA flux from facial injection sites to intracranial compartments, with transport occurring along maxillary–olfactory and temporomandibular–trigeminal neuro-lymphatic routes. I.d. delivery also resulted in accumulation within superficial lymph nodes, indicating engagement of peripheral immune compartments. ICP-MS gold element quantification revealed ∼20-fold higher gold accumulation in the brain and trigeminal nerve and lymph nodes within 12 hours following iontophoresis-assisted i.d delivery compared with passive i.d. (p<0.01). Silver staining of mouse brain histology sections confirmed SNA localization within the meninges, trigeminal nerve branches, maxillary sinus, and cortex. Furthermore, flow cytometry revealed decreased immunosuppressive myeloid populations and increased CD4+ and CD8+ T-cell activation across tumor, dura, and deep cervical lymph nodes. In combination with radiation, bi-SNA facial i.d. treatment significantly reduced tumor burden, enhanced antigen presentation in tumor microglia and myeloid cells, and increased PD-1 expression on T cells, supporting the potential of checkpoint inhibitor combinations. Conclusions: Iontophoresis-assisted facial intradermal delivery enables non-vascular CNS entry of bi-SNA nanotherapeutics by exploiting craniofacial neuronal and lymphatic brain border pathways. Citation Format: Akanksha S. Mahajan, Davin Hickman. Chow, Gaelen Clayton, Seunghyun Kim, Rachel Jarvis, Emma Shen, Clara Foltz, Cao Dai Phung, Eric Leuthardt, Alexander Stegh. Harnessing facial neuronal-lymphatic pathways for face-to-brain delivery of bimodal cGAS-STAT3 Spherical Nucleic Acids for anti-glioma therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A027.

Abstract Glioblastoma (GBM) is an aggressive brain cancer characterized by profound immunosuppression, largely driven by tumor-associated macrophages (TAMs), which account for 30-40% of the tumour bulk. In normal tissue homeostasis, macrophages detect, engulf, and clear stressed and cancerous cells through phagocytosis. TAMs, however, display markedly impaired ability to do so, and instead promote tumour growth. We sought to identify molecular pathways that regulate macrophage phagocytosis of GBM cells, with the goal of reprogramming TAMs into anti-tumor effectors. We performed a pooled genome-wide CRISPR knockout screen in BV2 macrophages. Mutagenized macrophages were co-cultured with murine glioma cells expressing ZsGreen, a fluorescent reporter. Upon phagocytosis, macrophages engulf ZsGreen and thus fluoresce, allowing for separation and collection of phagocytic and non-phagocytic macrophages by flow cytometry. Synthetic guide RNAs (sgRNAs) were recovered and sequenced to identify gene knockouts that enhanced phagocytosis. Analysis of sgRNA enrichment in ZsGreen+ macrophages revealed overrepresentation of gene knockouts involved in glycosaminoglycan biosynthesis, particularly the chondroitin sulfate pathway. Targeted disruption of CS biosynthesis genes in follow-up CRISPR knockout macrophage cell lines increased uptake of GBM cells in vitro, confirming CS synthesis loss enhances tumor cell phagocytosis. To contextualize these findings in GBM, we characterized O-glycan synthesis in patient tumors. We found CS synthesis gene programs are upregulated in GBM compared to normal brain tissue, and myeloid cells are the dominant producers of CS within the GBM niche. These data identify CS synthesis as a novel inhibitory pathway of macrophage phagocytic function in GBM. This work highlights glycosaminoglycan metabolism as a potential target for therapeutic reprogramming of TAMs to enhance innate immunity and immunotherapy efficacy in GBM. Citation Format: Shan Grewal, Vaseem Shaikh, Adrian Granda Farias, Kevin R. Brown, Lucas Asselstine, Mohamed Taleb, Chitra Venugopal, Patricia Mero, Jason Moffat, Sheila K. Singh. Genome-wide CRISPR screening identifies novel regulators of macrophage phagocytosis against glioblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A011.

Abstract Glioblastoma is the most aggressive primary malignancy of the central nervous system and remains uniformly fatal despite multimodal treatment. Its diffuse infiltrative growth, extensive genetic heterogeneity, and partial protection by an intact blood–brain barrier limit the effectiveness of current therapies, including maximal surgical resection followed by chemoradiation. Residual infiltrative tumor cells that escape resection and irradiation inevitably drive local recurrence, underscoring the need for therapeutic strategies capable of eradicating microscopic disease while sparing normal neural tissue. Targeted alpha therapy represents a transformative approach to internal radiation delivery, leveraging the high–linear energy transfer and short path length of alpha particles to induce lethal DNA damage in cancer cells with minimal collateral injury. Actinium-225 is particularly attractive due to its multi-alpha decay cascade; however, its clinical application is constrained by recoil-driven release of radioactive daughter nuclides, resulting in systemic redistribution and dose-limiting renal toxicity. Conventional chelator-based systems are unable to adequately retain these recoiling daughters following alpha emission. In this study, we developed a cyclodextrin-based supramolecular nanocarrier designed to both deliver actinium-225 and retain its radioactive progeny. Cross-linked cyclodextrin nanoparticles were synthesized and functionalized with bifunctional chelators to enable stable actinium complexation, while the polymeric architecture provided a secondary containment barrier for recoiling daughter isotopes. Physicochemical characterization confirmed nanoparticle dimensions and surface properties compatible with tumor accumulation and potential transport across biological barriers. Radiochemical analyses demonstrated high labeling efficiency and sustained radionuclide stability. Importantly, the cyclodextrin nanocarrier exhibited significantly enhanced retention of actinium daughter nuclides compared with conventional chelated constructs. In vitro evaluation using glioblastoma cell lines and patient-derived tumor stem cells demonstrated potent, dose-dependent cytotoxicity at picomolar concentrations. Alpha irradiation produced dense clusters of DNA double-strand breaks that were independent of oxygen availability, supporting efficacy in hypoxic tumor regions characteristic of glioblastoma. Collectively, these results demonstrate that cyclodextrin-based nanocarriers substantially improve the therapeutic index of actinium-225–based targeted alpha therapy by mitigating daughter nuclide recoil while preserving potent cytotoxic activity. This platform offers a promising strategy for safe and effective treatment of infiltrative glioblastoma and supports further preclinical development toward targeted and localized alpha-radiotherapeutic interventions. This abstract was refined using generative artificial intelligence for language clarity; all scientific content was reviewed and approved by the author. Citation Format: Punna Suryadevara. Supramolecular Sequestration of Actinium-225 via Cyclodextrin Nanopolymers: A Novel Strategy for Targeted Alpha Therapy in Glioblastoma Multiforme [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Immunol Res 2026;86(6_Suppl):Abstract nr A029.

Abstract Brain tumors are a leading cause of disability and death among children. Brain tumor treatments are often required for cure, but are damaging to brain tissue – particularly white matter, and is related to cognitive impairments for pediatric brain tumor survivors (PBTS). White matter tracts are critical for neural communication and supports cognition, including information processing speed, which underlies higher-order cognitive processes and is mediated by the brain’s default mode (DMN) and executive control (ECN) networks. It is unknown how white matter damage results in compromised information processing speed in PBTS. Thus, we explore the impact of DMN and ECN structural and functional connectivity on cognition during resting state, a visual-motor task, and through computational modeling. Forty-one healthy children and fifty-two PBTS were scanned at The Hospital for Sick Children. Tractography was conducted to examine DMN and ECN structural connectivity. MEG and measures of neural communication was conducted to examine DMN and ECN functional connectivity. Computational models were built using experimentally acquired structural connectomes to simulate functional connectivity. Partial least-squares path modeling was conducted to describe the relationship among white matter organization, neural communication, and information processing speed. Compared to healthy children, PBTS showed: slower information processing speed, DMN and ECN white matter compromise, and resting state DMN and ECN neural communication compromise that generalized to simulated and task-based neural synchrony compromise. Overall, DMN and ECN structural connectivity significantly influenced network neural communication and information processing speed, and white matter compromise had an indirect adverse impact on reaction time via perturbed neural synchrony. Our findings show an important connection between DMN and ECN connectivity that is essential for information processing speed. Further establishing alterations in DMN and ECN structural and functional connectivity as novel biomarkers of cognitive impairments could facilitate early intervention and monitoring of these deficits following brain tumor treatment. Citation Format: Noor Al Dahhan. Mechanisms of Cognitive Impairment in Children Treated for Brain Tumors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr PR006.

Abstract Introduction: Glioblastoma (GBM) is the most aggressive and lethal type of primary brain tumors, with a median survival time of only 12 to 15 months after diagnosis. Despite numerous research efforts, treatment options have remained largely unchanged for decades, with the Stupp Protocol combining surgery, radiotherapy, and chemotherapy remaining as the gold standard. This persistent poor prognosis underscores the need for novel therapy approaches. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene expression post-transcriptionally, have gained attention as potential therapeutic targets for GBM. Specifically, miR-92b is notably overexpressed in GBM tissue samples and GBM cell lines, contributing to tumor growth, resistance to treatment, and increased malignancy. Targeting miR-92b with Oligonucleotide MicroRNA Inhibitors (OMIs) has demonstrated promising tumor-suppressing effects in preclinical models. However, delivering these inhibitors efficiently across the blood-brain barrier (BBB) remains a significant challenge. To overcome this, we developed five modified Rabies Virus Glycoprotein (RVG) peptides that bind to α7 nicotinic acetylcholine receptors expressed on both BBB and GBM cells to facilitate targeted delivery. Methods: The wild-type and modified RVG peptide sequences were bound to liposomal nanoparticles to achieve targeted delivery. OMIs against miR-92b were then encapsulated inside RVG-functionalized liposomes, creating the lipid-based nanocarrier system. Results: GBM cells treated with modified RVG functionalized liposomes showed significantly enhanced uptake of the nanoparticle formulation compared to those treated with plain (non-functionalized) or RVG wild-type functionalized liposomes. This indicates that modifications of the RVG peptide enhance both cellular internalization efficiency and the downregulation of miR-92b. These results, along with high stability, are vital factors for successful therapeutic delivery. Conclusion: This study introduces a novel, targeted delivery platform capable of transporting stable miR-92b inhibitors directly to GBM cells. The modified RVG-functionalized gold liposomes offer a promising RNA-based therapeutic strategy for GBM, potentially paving the way for more effective treatments against this aggressive cancer. Citation Format: Diego E. Garcia Ortiz, Angel G. Rodriguez Monroig, Annelis O. Sanchez Alvarez, Fatma A. Valiyeva, Pablo E. Vivas Mejia. Modified RVG Functionalized Liposome Gold Nanoparticles for specific microRNA delivery Against Glioblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr A038.

Abstract Medulloblastoma (MB) is the most common malignant pediatric brain tumor, with some forms resistant to standard-of-care therapy. Therefore, novel drugs are needed that target different aspects of MB biology, including the proliferative and migratory properties of tumor cells. Using bioinformatic approaches, we demonstrate that the cytoskeletal scaffolding protein BAIAP2 is differentially expressed in MB compared to non-tumor brain cells, and overexpressed in MB and metastatic MB tissue compared to normal cerebellum. BAIAP2 interacts with the Rho GTPases CDC42 and RAC1, which have known roles in migration and invasion in multiple cell types. We demonstrate that BAIAP2 knockdown affects migration and invasion of MB cells. To characterize the BAIAP2 pathway further, we developed a small molecule screen using surface plasmon resonance (SPR) for compounds that bind BAIAP2. We discovered that the small molecule NSC678917 binds to BAIAP2 and inhibits MB cell viability and migration. Collectively, our studies suggest that the BAIAP2 pathway is a novel point of therapeutic intervention in MB. Citation Format: Luz C. Levanda-Sousa, Nitish Jangde, Robert Suter, Anna Jermakowicz, Jonathan Chu, Matthew D'Antuono, Mi-Hye Lee, Nagi Ayad. The BAIAP2 pathway regulates proliferation and migration in medulloblastoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Brain Cancer; 2026 Mar 23-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(6_Suppl):Abstract nr B001.