tbuckley/cabot-search huggingface dataset:
Abstract 3718: Characterization of chromosomal instability-related dependencies through cell-specific metric for gene dosage compensation potential
Authors: Péter Szikora, Ivan Fekete, María Victoria Ruiz-Pérez, Dóra Kállai, Csilla Hegedűs, Bence Szalai, Daniel Veres
Journal: Cancer Research (2025)

Abstract Numerical chromosomal instability (n-CIN) is a defining characteristic of most human cancers with serious implications of large-scale alterations of the genome - such as chromosome arm level copy number changes. These kinds of somatic alterations are frequently targeting oncogenes and tumor suppressors, enriched in cancer driver events in order to shape the transcriptome in favor of tumor progression and proliferation. While oncogenes are mostly associated with copy number gains and tumor suppressors are more frequent in chromosome arm losses, neighboring genes are also affected in both cases. This collateral damage may be able to create synthetic lethal relationships and context-specific dependencies. Cancer cells might be able to avoid partial loss and gain-related lethal effects by triggering different dose compensation mechanisms, occurring at the genomic, epigenetic and post-translational levels, which leads to deviations across copy number and expression profiles. To propose a metric for dose compensation potential, we analyzed copy number and gene expression profiles of the Cancer Cell Line Encyclopedia in order to characterize cancer cell lines with the ability to compensate dependencies arising from chromosomal losses and gains. Our metric consists of the sum of gene expression residuals from linear model fits, describing how much a cell line tends to under or overexpress genes compared to what we expect from copy number counts. By comparing other publicly available datasets with our results, such as perturbation transcriptomics data from the LINCS-L1000 project and the DepMap genome-wide gene essentiality measurements, we aim to identify CIN-related therapeutic vulnerabilities associated with chromosome arm losses and gains. Besides finding potential target candidates, we show that our method is capable of finding well-known pathway-specific compensation mechanisms. As an example, we show a significant correlation between the activity of the Nonsense mediated decay (NMD) pathway and our proposed compensation potential score (CPS) of cancer cell lines. We propose our method to be used to detect context-specific dependencies associated with gene dosage compensation, and also able to provide pathway-level evidence - both novel and previously known from the literature. Citation Format: Péter Szikora, Ivan Fekete, María Victoria Ruiz-Pérez, Dóra Kállai, Csilla Hegedűs, Bence Szalai, Daniel Veres. Characterization of chromosomal instability-related dependencies through cell-specific metric for gene dosage compensation potential [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 3718.
Abstract 1854: Neurotransmitter-derived lipid nanoparticles (LNPs) for brain-targeted drug delivery
Authors: Shuyu Wang
Journal: Cancer Research (2025)

The treatment of central nervous system (CNS) diseases, such as neurodegenerative disorders, brain tumors, brain infections, and stroke, is severely constrained by the blood-brain barrier (BBB) because it prevents the transfer of most of small-molecule drugs and macromolecules (e.g., peptides, gene drugs, and protein drugs) into the brain. We have developed a previously unknown class of neurotransmitter-derived lipidoids (NT-lipidoids) as simple and effective carriers for enhanced brain delivery of several BBB-impermeable cargos. Particularly, doping the NT-lipidoids into BBB-impermeable lipid nanoparticles (LNPs) gave the LNPs the ability to cross the BBB. Using this novel brain delivery platform, we successfully delivered small molecular drug, genes and proteins into the mouse brain via systemic intravenous administration. For example, the BBB-impermeable paclitaxel was delivered to the brain to treat glioma, and genome-editing fusion protein (−27)GFP-Cre recombinase was delivered for effective genome editing in neuronal cells of the Ai14 mouse brain through intravenous injection. Our recent results demonstrate that by doping the NT-lipidoids into BBB-impermeable clinical used liposome nanomedicines can give the nanomedicines the ability to cross the BBB to treat brain tumors and brain infections. We believe this NT-derived LNPs is a new, simple, universal, and effective brain delivery system, which may find wide applications in treating CNS diseases including brain tumors and providing a tool to study the brain function. Citation Format: Shuyu Wang. Neurotransmitter-derived lipid nanoparticles (LNPs) for brain-targeted drug delivery [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 1854.
Abstract 3778: Preclinical evaluation of BG-C137, a potential first-in-class FGFR2b-targeting ADC, for the treatment of FGFR2b-expressing cancer
Authors: Yibin Xu, Xiaolin Su, Qiming Xu, Mengran Qian, Taichang Zhang, Mei-Hsuan Tsai, Ruyue Ji, Junna Jiang, Bin Shao, Yuan Zhuang, Jiyuan Zhang, Xiaomin Song, Zhitao Wan, Xiaoyan Tang, Yue Wu, Charng-Sheng Tsai, Chichi Huang, Lai Wang, Zhirong Shen
Journal: Cancer Research (2025)

Fibroblast growth factor receptor 2b (FGFR2b, FGFR2IIIb), an alternative splicing isoform of FGFR2, is a receptor tyrosine kinases that activates multiple signaling cascades upon binding of FGFs, promoting cancer cell proliferation. It is also a tumor associated antigen overexpressed in multiple solid tumor types, especially gastric cancer (GC). Indeed, the clinical benefit of targeting FGFR2b has been demonstrated by Bemarituzumab, an Fc-enhanced monoclonal antibody in combination with chemotherapy in first-line FGFR2b-expressing gastric cancer. Here, we report the preclinical characterization of BG-C137, a first-in-class FGFR2b antibody conjugated with a topoisomerase inhibitor. In contrast to Bemarituzumab, which functions through antibody dependent cellular phagocytosis/cytotoxicity and sustained signaling blocking function, BG-C137 introduces direct toxin killing to enhance the tumor inhibition with strong bystander effect to overcome the heterogeneity of FGFR2b expression. Upon antigen engagement, BG-C137 was rapidly internalized and potently killed tumor cells with diverse FGFR2b expression level. Single dose of BG-C137 showed strong anti-tumor efficacy in vivo, including FGFR2b-amplified and non-amplified models. It also demonstrated strong bystander killing effect in vitro and maintained strong anti-tumor efficacy in models with heterogeneous FGFR2b expression. Additionally, we showed that corneal dystrophy, which might correlate with corneal toxicity of Bemarituzumab in the clinic, was caused by its complete signaling blocking function. Whereas BG-C137, with weaker blocking function, spared corneal dystrophy in mice as well as in non-human primates, even at high doses. With its differentiated targeting strategy, BG-C137 is not only a first-in-class FGFR2b ADC but also holds the potential to pursue the best-in-class opportunity in FGFR2b targeting treatments. Together, these observations support the clinical development of BG-C137 for the treatment of FGFR2b-expressing tumors (ClinicalTrials.gov ID NCT06625593). Citation Format: Yibin Xu, Xiaolin Su, Qiming Xu, Mengran Qian, Taichang Zhang, Mei-Hsuan Tsai, Ruyue Ji, Junna Jiang, Bin Shao, Yuan Zhuang, Jiyuan Zhang, Xiaomin Song, Zhitao Wan, Xiaoyan Tang, Yue Wu, Charng-Sheng Tsai, Chichi Huang, Lai Wang, Zhirong Shen. Preclinical evaluation of BG-C137, a potential first-in-class FGFR2b-targeting ADC, for the treatment of FGFR2b-expressing 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 3778.
Abstract 1088: LiverSCA 2.0: An enhanced and comprehensive cell atlas of human hepatocellular carcinoma, intrahepatic cholangiocarcinoma and metabolic dysfunction-associated steatotic liver disease/steatohepatitis
Authors: Fanhong Zeng, Renwen Long, Tina Suoangbaj, Irene Oi-Lin Ng, Daniel Wai-Hung Ho
Journal: Cancer Research (2025)

Abstract Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two distinct types of primary liver cancer (PLC) characterized by a considerable degree of cellular and molecular heterogeneity. We recently developed a web-based cell atlas called LiverSCA with a user-friendly interface, comprehensive functionality, and a complete set of analytical pipelines. In the previous version, LiverSCA includes 40 subjects (35 HCC patients with various etiological risk factors and five healthy controls) with a total cell count of more than 140, 000 cells. It facilitates the exploration of gene expression patterns, cellular composition, and intercellular communication in the liver and PLC tumor microenvironment, aiming to help researchers discover new mechanistic insights into the complex tumor microenvironment of HCC. To further enhance the comprehensiveness of LiverSCA, we have expanded its catalog with additional datasets of different phenotypes/subtypes of liver and PLC, such as intrahepatic cholangiocarcinoma (ICC) and metabolic dysfunction-associated fatty liver disease/steatosis (MASLD/MASH). The current enhanced version of the LiverSCA cell atlas contains six phenotypes (normal, HBV-HCC, HCV-HCC, non-viral HCC, ICC, and MASH), encompassing 63 patients and more than 248, 000 cells. In addition, we have incorporated a comparative visualization method that allows users to simultaneously examine and compare gene expression levels between two different phenotypes. We are committed to the continued development of LiverSCA to narrow the knowledge gap between different research fields and accelerate knowledge transfer in the scientific community. We envision that it will become a valuable resource that supports researchers to conveniently study the cellular and molecular landscape of the liver and PLCs. In addition, as scRNA-seq technology is still rapidly evolving, more features, such as spatial transcriptomics and multimodal omics, will be considered in future updates. Citation Format: Fanhong Zeng, Renwen Long, Tina Suoangbaj, Irene Oi-Lin Ng, Daniel Wai-Hung Ho. LiverSCA 2.0: An enhanced and comprehensive cell atlas of human hepatocellular carcinoma, intrahepatic cholangiocarcinoma and metabolic dysfunction-associated steatotic liver disease/steatohepatitis [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 1088.
Abstract 2070: Subcellular mapping of immune repertoire profiles with <i>in situ</i> sequencing on G4X
Authors: Michael J. Lawson, Tung T. Le, Zane Hiatt, Ryan Shultzaberger, Kenneth Gouin, Daan Witters, Eli N. Glezer
Journal: Cancer Research (2025)

Abstract Detailed spatial analysis of immunology and pathology, such as immune repertoire profiling in tissue, requires in situ sequencing of variable gene regions. We introduce Direct-Seq, a novel technology using the G4X platform for in situ RNA sequencing at sub-cellular resolution, demonstrated by sequencing IgH and TCRB receptors in PBMCs and FFPE tissue. We developed a probe panel that targets the conserved V and J-regions that flank CDR3 on IgH transcripts and a second panel that targets the V and C-regions that flank CDR3 and J regions on TCRB transcripts. PBMCs were seeded onto a glass substrate, followed by fixation. The diverse gap sequence was reverse transcribed into the probes, which were then clonally amplified. Clonal amplification products were sequenced in situ using Singular Genomics’ SBS chemistry. We also applied the technique to tissue samples by transferring 5-µm thick FFPE tonsil sections to G4X slides, followed by deparaffinization and antigen retrieval. Amplicon preparation and sequencing were conducted in the same way as for PBMCs. Direct-Seq successfully profiled ∼ 60% of all B-cells (relative to CD19-positive fraction) and ∼ 20% of all T-cells (relative to CD3-positive fraction) in PBMC populations. We observed the expected high diversity of clonotypes, with 92-98% of B and T-cells having distinct CDR3 sequences. Comparing multiple 50 bp reads within the same cell, we calculate the sequencing accuracy to be ∼ 98%. For cells that had at least 1 read, we detected on average ∼ 6 reads/cell for B-cells and ∼ 2 reads/cell for T-cells. For FFPE tonsil samples we observed similar levels of diversity (94-99%) and accuracy (97-99%) as we did in PBMCs, but the detection efficiency was significantly lower, likely due to reduced RNA accessibility and degradation resulting from fixation. In conclusion, Direct-Seq has demonstrated its unique capability for in situ sequencing of variable regions of IgH and TCRB transcripts in both PBMCs and FFPE tissues. This technology enables detailed mapping of immune cell clonality and diversity, providing a powerful tool for advancing our understanding of immunity and disease. Citation Format: Michael J. Lawson, Tung T. Le, Zane Hiatt, Ryan Shultzaberger, Kenneth Gouin III, Daan Witters, Eli N. Subcellular mapping of immune repertoire profiles with in situ sequencing on G4X [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 2070.
Abstract 2327: Boosting cancer vaccine efficacy with Vitamin E for immunoprevention of ER- breast cancer
Authors: Yi Xiao, Yuan Zhang, Yunhai Li, dihua Yu
Journal: Cancer Research (2025)

Abstract Estrogen receptor negative (ER-) breast cancers have worse prognoses with no effective prevention strategies. Developing safe and effective tactics for immunoprevention of poorly immunogenic breast cancers is highly challenging. Recently, we found that vitamin E (VitE) stimulates dendritic cell (DC) functions and potentiates anti-tumor immunity of immunotherapies. Here, we explored whether VitE can enhance anti-tumor immunity of cancer vaccines for immunoprevention of ER- breast cancer. Indeed, VitE, delivered as a vaccine adjuvant, significantly increases dendritic cell antigen presentation and boosts potent antigen-specific T cell responses. We noted that local injection of VitE with vaccines yielded substantially higher efficacy than oral VitE administration Moreover, compared to the vehicle-treated and vaccine only groups, VitE, given as vaccine adjuvants, significantly delayed tumor outgrowth and extended tumor-free survival in multiple mammary tumor transplantation models and in spontaneous mammary tumor model of MMTV-neu transgenic mice, whereas anti-PD1 administration showed a marginal effect in these tumor models. Mechanistically, in addition to targeting DC checkpoint SHP1, VitE fosters antigen uptake, increases co-stimulatory molecules CD80/CD86/CD40 expression and downregulates PD-L1 in DCs, that ultimately boosts antigen-specific effector/memory T cells. Furthermore, VitE administration altered landscapes of CD8+ effector T cells and fostered their transition to memory T cells. Together, our study demonstrates that VitE potentiates cancer vaccine efficacy via DCs and memory T cells, thus can be given as a safe and effective adjuvant of cancer vaccine for immunoprevention of ER- breast cancer. Citation Format: Yi Xiao, Yuan Zhang, Yunhai Li, dihua Yu. Boosting cancer vaccine efficacy with Vitamin E for immunoprevention of ER- breast 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 2327.
Abstract 1874: Glycoproteome and surfaceome mapping of epithelial-to-mesenchymal transition reveals key ion channel regulation and novel biomarkers in cancer metastasis
Authors: Xing Xu, Kejun Yin, Ronghu Wu
Journal: Cancer Research (2025)

Abstract The epithelial-to-mesenchymal transition (EMT) is a crucial process driving cancer metastasis. In this transition, cell morphologies and properties are dramatically changed, but the underlying molecular mechanisms remain to be explored. In this work, we performed a comprehensive analysis of the proteome, the glycoproteome, and the surfaceome during the EMT process induced in A549 lung carcinoma cells using mass spectrometry-based proteomics. We identified five distinct EMT states characterized by alterations in protein expression and N-glycosylation patterns. We characterized 8,891 proteins, including 1,366 N-glycoproteins and 635 surface glycoproteins, and further bioinformatic analyses provide valuable insights into the mechanisms of EMT. Notably, we observed significant regulation of sodium, chloride, and calcium ion channels during EMT, underscoring their importance in cancer metastasis. Surface glycoproteins such as MET and SLC2A1 emerged as potential biomarkers for partial EMT, paving the way for advancements in early cancer diagnosis and targeted therapies. Furthermore, our findings reveal that EMT-associated N-glycosylation occurs in specific protein domains and aggregation-prone regions (APRs), affecting protein stability and trafficking. This work advances our understanding of the molecular mechanisms of EMT and underscores the therapeutic potential of targeting glycoproteins and ion channels in metastatic cancer. Citation Format: Xing Xu, Kejun Yin, Ronghu Wu. Glycoproteome and surfaceome mapping of epithelial-to-mesenchymal transition reveals key ion channel regulation and novel biomarkers in cancer metastasis [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 1874.
Abstract 1537: The extracellular matrix supports pancreatic cancer cell growth under nutrient deprivation
Authors: Ifeoluwa Feyisayo Oyelade, Elena Rainero
Journal: Cancer Research (2025)

Abstract Pancreatic cancers have a poorly vascularized and nutrient-deficient microenvironment making them more susceptible to nutrient deprivation. Evidence has shown that Pancreatic Ductal Adenocarcinoma (PDAC) cells survive in a nutrient-deprived and hypovascular microenvironment. Here, we investigate the roles of the Extracellular Matrix (ECM) in supporting the growth of PDAC cells in different nutrient-deprivation conditions. Our cell proliferation, microscopy and targeted Mass Spectroscopy metabolomics data showed that Matrigel, but not collagen I, supports the proliferation of PDAC cells in Glucose and Glutamine deprivation conditions, as well as in Tissue Interstitial Fluid Media (TIFM), which has been reported to mimic the physiological nutrient availability in PDAC tumors. In addition, we found that the role of Matrigel in supporting the growth of pancreatic cancer cells is linked to increasing cell proliferation rather than reducing cell death. Importantly, our Targeted Mass spectrometry metabolomics data showed that the Arginine metabolism is upregulated when the cells are grown under starvation on Matrigel compared to plastic. We have identified some genes that are likely to play a role in the upregulation of this metabolic pathway and we are currently using qPCR and Western blotting techniques to identify whether the ECM and/or nutrient availability affect their expression. Finally, we will determine their role in promoting ECM-dependent PDAC cell proliferation under starvation. Overall, our study has established that the ECM can alter the metabolism of PDAC cells to support their cell growth under nutrient-limiting conditions. Citation Format: Ifeoluwa Feyisayo Oyelade, Elena Rainero. The extracellular matrix supports pancreatic cancer cell growth under nutrient deprivation [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 1537.
Abstract 1853: BIK-E715E, an integrin-targeting ligand-drug conjugate equipped with a novel drug delivery system, demonstrates enhanced antitumor efficacy in glioblastoma
Authors: Kideok Shin, Hyunju Sung, Jae Ho Jung, Sang Eun Kim
Journal: Cancer Research (2025)

We developed a novel drug delivery system ELiTE-DDS, designed to enhance target-selective intracellular delivery of therapeutic agents, where ELiTE stands for enhancing ligand targeting and endocytosis. Integrins αvβ3 and αvβ5, highly expressed in glioblastoma tumor cells, are molecular targets for glioblastoma treatment. In this study, we applied the ELiTE-DDS platform to a conjugate consisting of a high-affinity integrin αvβ3/αvβ5-binding ligand, D-[c(RGDfK)]2, and a topoisomerase I inhibitor exatecan, yielding BIK-E715E as a drug candidate for glioblastoma. BIK-E715E exhibited high selectivity and binding affinities for integrins αvβ3 and αvβ5 and was internalized through an Arf6-dependent, dynamin-independent endocytic pathway. Cellular treatment with BIK-E715E produced PARP cleavage and phosphorylation of Chk1 and histone H2AX, indicating drug-induced apoptosis and DNA damage, respectively. There was significant translocation of BIK-E715E in a hCMEC/D3 in vitro blood-brain barrier (BBB) model, suggesting its receptor-mediated transcytosis across the BBB. In U87MG subcutaneous and orthotopic xenograft mouse models, BIK-E715E accumulated in tumors with high efficiency and resulted in marked inhibition of tumor growth, which was greater than exatecan-induced growth inhibition. These data demonstrate that BIK-E715E is an attractive drug candidate for glioblastoma, equipped with a novel drug delivery system. Further, they also suggest that our ELiTE-DDS platform has great potential for enhancing target-selective intracellular delivery of therapeutic agents across the BBB. Citation Format: Kideok Shin, Hyunju Sung, Jae Ho Jung, Sang Eun Kim. BIK-E715E, an integrin-targeting ligand-drug conjugate equipped with a novel drug delivery system, demonstrates enhanced antitumor efficacy in glioblastoma [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 1853.