tbuckley/cabot-search huggingface dataset:
Abstract 68: Precision medicine in glioblastoma: cortical network disruptions, biomarker development, and multimodal therapeutic strategies
Authors: Tenesha Connor, Frederick Bell, Macit Emre Lacin, Miguel Maldonado, Kemal Ozdemirli, Anthony Sloan, Justin Lathia, Murat Yildirim
Journal: Cancer Research (2025)

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.
Abstract 3000: Targeting ERK and PI3K signaling in pancreatic ductal adenocarcinoma
Authors: Gauthami Nair, Katie Reindl, Mohiuddin Quadir
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a dismal five-year survival rate of only 13%. The high mortality is largely due to late-stage diagnosis, limited surgical options (available in just 10-20% of cases), and the failure of current chemotherapy regimens, which are often plagued by toxicity and drug resistance. Therefore, innovative therapeutic strategies targeting key signaling pathways driving tumor progression are urgently needed. Mutations in the KRAS gene, present in approximately 95% of PDAC cases, lead to hyperactivation of the KRAS protein and downstream pathways, including extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K). In this study, we hypothesized that simultaneous inhibition of these critical pathways could effectively suppress PDAC cell proliferation. Using SCH772984 (an ERK 1/2 inhibitor) and pictilisib (a class I PI3K inhibitor), we evaluated their combined effects on human PDAC cell lines (MIA PaCa-2 and PANC-1) and a patient-derived xenograft (PDX) cell line. Our results demonstrate significant synergy between these two inhibitors, as evidenced by reduced cell viability and colony formation in clonogenic assays compared to single-agent treatments. Western blot analysis confirmed that SCH772984 was able to inhibit its target ERK 1/2 and pictilisib was able to inhibit AKT, that is downstream of PI3K. These findings suggest that dual targeting of ERK and PI3K pathways effectively disrupts PDAC cell growth. Future studies will focus on formulating these inhibitors into nanoparticle-based drug delivery systems to enhance solubility, stability, and tumor-specific delivery. Additionally, preclinical testing in animal models will provide critical insights into the therapeutic potential of this combination. This approach represents a promising avenue for improving PDAC treatment outcomes and addressing unmet needs in this aggressive disease. Citation Format: Gauthami Nair, Katie Reindl, Mohiuddin Quadir. Targeting ERK and PI3K signaling in pancreatic ductal adenocarcinoma [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 3000.
Ampullary Adenoma and Hepatic Inflammatory Pseudotumor Mimicking Malignancies on 18F-FDG PET/CT
Authors: Qingqing Han, Xiaoyan Chang, Wuying Cheng
Journal: Clinical Nuclear Medicine (2025)

We report a rare case of ampullary tubulovillous adenoma with secondary jaundice and hepatic inflammatory pseudotumor mimicking malignancies on 18 F-FDG PET/CT. A 68-year-old woman presented with fever, jaundice and abdominal pain. Serum tumor markers (CEA, AFP, CA19-9, CA125, and CA242) were normal, except for a mild elevation CA72-4. 18 F-FDG PET/CT revealed biliary obstruction, hypermetabolic foci in the descending duodenum, and a hepatic mass, initially suggesting ampullary adenocarcinoma with hepatic metastasis. Post-surgery pathology confirmed ampullary tubulovillous adenoma and hepatic inflammatory pseudotumor.
Abstract 164: Heterogeneous dormant breast cancer cells leverage bone marrow cell plasticity at the single-cell level to drive metastasis initiation
Authors: Noriko Gotoh
Journal: Cancer Research (2025)

Abstract Breast cancer remains a leading cause of cancer-related deaths among women worldwide, largely due to the high risk of recurrence and metastasis in HER2-negative and hormone receptor-negative triple-negative breast cancer (TNBC) patients. While bone metastasis is common, the molecular mechanisms driving its initiation remain poorly understood. We recently identified a subpopulation of cancer stem cells (CSCs) with ancestral features, marked by the FXYD domain-containing ion transport regulator 3 (FXYD3), a Na+/K+ pump component. These “ancestor-like CSCs” persist in breast tissues during neoadjuvant chemotherapy (NAC), linking them to drug-tolerant persisters (DTPs) and positioning them as critical therapeutic targets for preventing local recurrence (Li M, Gotoh N et al., J Clin Invest, 2023). Despite this, the mechanisms underlying DTP dormancy in the bone marrow and their transformation into bone metastasis-initiating cells remain unclear. Given the stromal richness of TNBC tissues, we explored interactions between cancer-associated fibroblasts (CAFs) and breast cancer cells using a co-culture system. Single-cell analysis revealed a strong upregulation of granulocyte colony-stimulating factor (GCSF) in co-cultured CAFs. Notably, we identified FXYD3+ and GCSF receptor-positive cancer cells as a distinct subpopulation of CSCs with bone metastasis initiation potential. To investigate the temporal-spatial dynamics of bone metastasis initiation, we performed single-cell RNA sequencing (10x Genomics) and multiplex immunofluorescent imaging (PhenoCycler) using metastatic bone marrow from the patient-derived xenograft (PDX) models. These analyses revealed how bone metastasis-initiating CSCs exploit the plasticity of bone marrow cells—particularly hematopoietic and mesenchymal stem cells—to establish a CSC niche at the single-cell level. Our findings provide critical insights into the mechanisms of recurrence and metastasis in breast cancer, offering novel therapeutic opportunities to target ancestor-like CSCs and prevent disease progression. Citation Format: Noriko Gotoh. Heterogeneous dormant breast cancer cells leverage bone marrow cell plasticity at the single-cell level to drive metastasis initiation [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 164.
Abstract 299: Characterization of a senescence phenotype induced by advanced glycation end products in prostate cancer
Authors: Luisa Bacca, Tarek Hallal, Carole Luthold, Nadia Boufaied, François Bordeleau, David Labbé
Journal: Cancer Research (2025)

Prostate cancer (PCa) represents a worldwide leading cause of cancer-related mortality in men. Diabetes is also a highly prevalent and a rapidly growing pathology. Intriguingly, diabetes is associated with decreasing PCa incidence, and at the same time, it is linked to increased mortality rates for men already afflicted by the disease. A plausible mediator causing this effect are Advanced Glycation End Products (AGEs), products of the Maillard reaction, occurring between sugars and proteins at body temperature. AGEs, known to be elevated in diabetic patients, have been reported to increase the Extracellular Matrix (ECM) stiffness via ECM-crosslinking, potentially explaining the tumor-promoting effects of diabetes in cancer progression. Nonetheless, the protective role of diabetes in prostate cancer is not yet fully understood. Interestingly, we demonstrated that AGEs, produced by mixing sugars and an abundant circulating protein in the blood decreased PCa cell proliferation in vitro in a dose-dependent and irreversible manner across a panel of human PCa cell lines. Importantly, through transcriptomic analysis, we found that AGEs-mediated cell proliferation blocking correlate with a senescence transcriptional signature. Accordingly, treatment with AGEs lead to increased beta-galactosidase activity, a hallmark of senescence, and to the upregulation of senescent markers linked to cell cycle arrest (p21WAF1/Cip1) and pro-inflammatory cytokines (IL-8) at the transcriptional and translational levels. We also confirmed the expression of the senescence-associated secretory phenotype (SASP, e.g., IL, CXCL, CCL) in AGEs-treated PCa cells. Finally, our validation of key transcriptomics analysis confirmed the upregulation of HMOX1, an enzyme reported to be induced during cellular senescence, upon AGEs treatment. Altogether, our results suggest that AGEs-mediated senescence could underlie the lower incidence of PCa among diabetic patients. This sets the stage for combination treatments between AGEs and senolytics, drugs that selectively target and induce cell death in senescent cells, as a novel therapeutic strategy in PCa. Citation Format: Luisa Bacca, Tarek Hallal, Carole Luthold, Nadia Boufaied, François Bordeleau, David Labbé. Characterization of a senescence phenotype induced by advanced glycation end products in prostate cancer [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 299.
Abstract 41: Generation and multiomic profiling of a<i>APC/TP53</i>double knockout normal colon organoid
Authors: Younghee Choi, Eunju Kim, Jihyun Park, Sang-Hyun Song, Tae-You Kim
Journal: Cancer Research (2025)

Abstract Colorectal cancer frequently arises from early tumorigenic events driven by mutations in the APC and TP53 genes. To elucidate mechanisms underlying early colon tumorigenesis, we established normal colon organoids with APC and TP53 double knockouts (DKO). Through integrated multi-omics analyses, including RNA-seq, ATAC-seq, methylation-seq, and H3K27ac ChIP-seq, we identified significant upregulation of the KIT gene in DKO organoids compared to controls. Subsequent KIT knockout generated APC/TP53/KIT triple knockout (TKO) organoids, which exhibited markedly reduced migratory capacity and Ki-67 tumor intensity, highlighting a pivotal role for KIT in early tumorigenic processes. Proteomic analysis further revealed that GSK3β phosphorylation was significantly reduced in TKO organoids compared to DKO organoids, suggesting a mechanistic link between KIT expression and downstream signaling pathways critical for early tumor progression. Notably, treatment with the KIT inhibitor imatinib phenocopied the effects of KIT knockout, reinforcing KIT's role as a driver of early colon tumorigenesis. These findings provide critical insights into the molecular mechanisms of early tumorigenesis in APC and TP53 mutant contexts, identifying KIT as a promising therapeutic target for intervention in early-stage colorectal cancer. Citation Format: Younghee Choi, Eunju Kim, Jihyun Park, Sang-Hyun Song, Tae-You Kim. Generation and multiomic profiling of aAPC/TP53double knockout normal colon organoid [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 41.
Abstract 613: Investigating cyclooxygenase isoforms as targets for anticancer compounds isolated from Tulbaghia violacea
Authors: Zodwa Dlamini, Rodney Hull, Mohammed Alaouna
Journal: Cancer Research (2025)

Abstract Introduction: The medicinal plant Tulbaghia violacea exhibits anticancer properties in triple-negative breast cancer (TNBC) cells, primarily through apoptosis induction. Transcriptomic analyses of treated TNBC cells highlighted altered expression of cyclooxygenase isoforms COX-1 and COX-2. COX-1, with anti-apoptotic properties, is associated with tumor progression, while COX-2, with pro-apoptotic properties, acts as a tumor suppressor. Methods: Bioactive compounds derived from T. violacea were screened for their potential interaction with cyclooxygenase isoforms using molecular docking approaches. Protein structures for COX-1 (PDB: 6Y3C) and COX-2 (PDB: 5IKT) were retrieved from the Protein Data Bank. Ligand and protein preparation for sixteen compounds was conducted using the Schrödinger Suite. Standard precision (SP) docking was followed by MM-GBSA post-docking and extra precision (XP) docking to refine binding affinity predictions. Results and Discussion: COX-2 demonstrated the highest average docking scores, indicating stronger binding affinity for the T. violacea-derived compounds. Comparative structural analysis revealed significant differences in binding site residues and global backbone structures between COX-1 and COX-2. SiteMap analysis identified the most druggable regions, with COX-2’s larger binding pocket enabling higher binding affinity. Notably, the same compounds were capable of binding both isoforms, although with lower affinity for COX-1. These findings suggest that the anticancer activity of T. violacea compounds may be mediated by their preferential binding to COX-2, which is often upregulated in cancers. Conclusion : This study highlights the potential of Tulbaghia violacea as a source of bioactive compounds targeting cyclooxygenase isoforms, particularly COX-2. The preferential binding to COX-2 aligns with its pro-apoptotic role and its upregulation in cancers, underscoring its relevance in cancer therapy. Further experimental validation is warranted to confirm these in silico findings and to explore the therapeutic potential of T. violacea-derived compounds. Citation Format: Zodwa Dlamini, Rodney Hull, Mohammed Alaouna. Investigating cyclooxygenase isoforms as targets for anticancer compounds isolated from Tulbaghia violacea [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 613.
Abstract 302: Study of treatment-induced senescence in head and neck squamous cell carcinoma according to HPV status
Authors: Karim Bouhjar, Carine Michiels, Francis Rodier
Journal: Cancer Research (2025)

Abstract Introduction: Head and neck cancer (HNC) is the sixth most common cancer worldwide, with an incidence of approximately 600, 000 new cases each year. Within this type of cancer, two main categories should be distinguished: HPV-negative and HPV-positive tumors. In this context, the tumorigenesis process differs, and the prognosis associated with each subtype is variable. Despite this difference, the therapeutic management of patients is identical. The aim of this research project is to demonstrate that this management should take HPV status into account and that the associated treatments must be adapted accordingly. Indeed, preliminary results show that depending on the HPV status, the response to treatments induces either a pro-apoptotic or pro-senescence response. This research project therefore investigates the biological and molecular mechanisms by which the HPV status influences cell fate decisions following treatment. Materials and Methods: Different characteristics of senescent cells have been assessed; morphology, positivity for SA-β-gal, SASP expression, cell cycle assessment and proliferation. The preliminary results suggest an induction of cellular senescence in most of the cell lines following treatment. Following this, a new aspect of the thesis has been recently opened through a mass spectrometry approach. In parallel, HPV-negative cell lines expressing key viral factors are currently being generated to create a more relevant model, combined with the use of patient tissues that will be analyzed by multiplexed immunofluorescence. Discussion: The first results have fully characterized the induction of the senescent phenotype following treatment, depending on HPV status, in head and neck cancer cell lines. The unbiased proteomic approach will help to identify promising candidates involved in this senescence induction according to HPV status. Simultaneously, access to the CrCHUM biobank will allow testing of the various hypotheses in situ. Citation Format: Karim Bouhjar, Carine Michiels, Francis Rodier. Study of treatment-induced senescence in head and neck squamous cell carcinoma according to HPV status [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 302.
Abstract 196: Acetylcholine enhances HIF-1α expression in pancreatic cancer cells under hypoxia through nAchR-α7/PDPK1/YAP signaling pathway
Authors: Yunmi Cho, Eun-Taex Oh, Ha Gyeong Kim, Heon Joo Park
Journal: Cancer Research (2025)

Abstract The pancreas has a high distribution of the autonomic nervous system. The role of the autonomic nervous system in pancreatic ductal adenocarcinoma development has been addressed in recent studies. HIF-1 regulates the expression of genes involved in angiogenesis, metastasis, tumor growth, chemoresistance and radioresistance, underscoring the growing interest in targeting HIF-1 for cancer control. In this study, we investigated the molecular mechanisms underlying the neurotransmitter acetylcholine-enhanced HIF-1α expression in pancreatic cancer cells under hypoxia, leading to the growth of pancreatic cancer organoids. In vitro assays showed that, under hypoxic conditions, acetylcholine caused a concentration-dependent increase in nAChR-α7-mediated HIF-1α expression, enhancing expression of its target genes in pancreatic cancer cells. We further found that acetylcholine increased HIF-1α protein stability in pancreatic cancer cells under hypoxic conditions. This effect was mediated by PDPK1/YAP signaling pathway, as evidenced by the fact that acetylcholine-induced enhancement of HIF-1α expression was blocked by siRNA-mediated knockdown of PDPK1/YAP signaling pathway. Consistent with these findings, an investigation of the relationship between nAChR-α7 and clinicopathological features in pancreatic cancer patients using publicly available datasets showed that high levels of nAChR-α7 are correlated with a poorer prognosis in pancreatic cancer patients. Subsequently, nAChR-α7 specific inhibitor α-bungarotoxin efficiently inhibited the acetylcholine-induced increase of growth of pancreatic cancer organoids under hypoxia. Collectively, these findings identify novel mechanisms by which acetylcholine enhances HIF-1α expression through PDPK1/YAP signaling pathway and provide further evidence that HIF-1α is a potential anticancer target in acetylcholine-associated pancreatic cancer. Citation Format: Yunmi Cho, Eun-Taex Oh, Ha Gyeong Kim, Heon Joo Park. Acetylcholine enhances HIF-1α expression in pancreatic cancer cells under hypoxia through nAchR-α7/PDPK1/YAP signaling pathway [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 196.
Abstract 868: Platform for purifying serially cytotoxic T cells: advancing cell engineering and in vivo applications
Authors: Eric Ferguson, John M. Beierle, Behrad Azimi
Journal: Cancer Research (2025)

Abstract Current techniques for the enrichment of engineered T cells rely on surface markers that do not accurately capture a T cell’s exhibited cytotoxicity, specificity for antigens, or its temporal state in the activation-exhaustion cycle. While microscopy-based methods have been developed to assay live T cells based on their interaction and cytotoxicity against antigen-presenting cells (APCs), no single technique can isolate serially cytotoxic T cells based on the frequency and the cytotoxic outcome of their interaction with specific APCs. The addition of an isolation step based on cell behavior is imperative for pooled screening for optimized engineering of T-cells as well as for the utilization of the enriched cells in vivo. Narwhal Bio Inc.'s A1 platform, an instrument, software, and reagent combination, seeks to overcome this challenge by in vitro cell identification, tagging, and downstream isolation of live cells based on behaviors assessed through microscopy. This live-cell-in, live-cell-out process could enable downstream applications like animal studies, further cell engineering, and multiomics drug and target discovery. We have applied this system to enrich CAR-T cells involved in repeated cytotoxic events. We assayed and tagged T cells based on their serial cytotoxicity in an APC co-culture in real time. We then isolated the tagged T cells, assessed their activation state using CD69 and CD25, and confirmed enrichment for the CAR representation in the more cytotoxic cell population. We assessed the potency of the enriched T cells after sorting, culture, and subsequent co-culture with APCs, showing &amp;gt;3x improvement in potency. Lastly, we illustrated how the process can be performed on the order of millions of cells in a day for various in vivo and in vitro downstream applications, including pooled screening of T-cell engineering and use in animal models. Citation Format: Eric Ferguson, John M. Beierle, Behrad Azimi. Platform for purifying serially cytotoxic T cells: advancing cell engineering and in vivo applications [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 868.