tbuckley/cabot-search huggingface dataset:
Abstract 3727: Physical activity patters according to demographic, social, and clinical correlates among breast cancer survivors
Authors: Michael Kebede, Charles E. Matthews, Matthew R. Dunn, Natasha R. Burse, Annie G. Howard, Kelly R. Evenson, Melissa A. Troester
Journal: Cancer Research (2025)

Abstract INTRODUCTION: Moderate to Vigorous Physical Activity (MVPA) after breast cancer diagnosis is associated with improved survivorship, suggesting the need for interventions to increase MVPA. However, differences in MVPA by race and age among breast cancer survivors are not well described in population-based studies. METHODS: We analyzed data from Carolina Breast Cancer Study Phase 3 (CBCS3, n =2994, 50% Black) participants to evaluate the trajectory of MVPA up to 18-month post-diagnosis. Participants were classified as having Any MVPA (and Sufficient or Insufficient according to national guidelines) or No MVPA. Associations between MVPA and demographic, social, and clinical variables were estimated using multivariable logistic regression. RESULTS: At baseline, 84.0% of participants reported Any MVPA pre-diagnosis, which dropped to 55.4% at 6-month post-diagnosis, then rebounded to 85.1% by 18-month post-diagnosis. Among those who had No MVPA pre-diagnosis, 32.5% and 71.0% became active at 6- and 18-month post-diagnosis, respectively. Race was not significantly associated with Any MVPA [OR =1.12, 95%CI (0.90, 1.39) Non-black vs. Black], but higher income [OR =1.33, 95%CI (1.02, 1.74) &amp;gt;$30K vs. &amp;lt;15K], lower Body Mass Index (BMI) [OR = 1.30, 95%CI (1.00, 1.73) &amp;lt;25 vs. &amp;gt;30], low area deprivation [OR = 1.35, 95%CI(1.08, 1.67) vs. high], high area assets [OR =1.54, 95%CI (1.23, 1.93) vs. low], and stage I [OR = 1.72, 95%CI(1.22, 2.43) vs. 3 or 4], were associated with Any MVPA at 18-month post-diagnosis. CONCLUSION: Individual and community-level socio-economic status (SES) are strong predictors of Any MVPA, and together with established clinical correlates (such as late disease), these factors may contribute to breast cancer disparities. Citation Format: Michael Kebede, Charles E. Matthews, Matthew R. Dunn, Natasha R. Burse, Annie G. Howard, Kelly R. Evenson, Melissa A. Troester. Physical activity patters according to demographic, social, and clinical correlates among breast cancer survivors [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 3727.
Abstract 1559: Assessing efficacy of anti-glypican-1antibody-drug conjugate as potential therapeutic approach for gastric cancer
Authors: Yuji Suzuki, Satoshi Serada, Kota Kawabata, Tsuyoshi Takahashi, Yuichiro Doki, Tetsuji Naka
Journal: Cancer Research (2025)

Abstract Background: Despite significant advancements in cancer treatment, gastric cancer (GC) still has a high incidence and mortality rate. Antibody-drug conjugates (ADCs) are emerging as viable treatment option for GC. We previously identified glypican-1 (GPC1) as a novel cancer antigen in esophageal squamous cell carcinoma using quantitative protein expression profiling analysis focused on plasma membrane proteins, and recognized it as a potential target for ADCs.Glypican-1 (GPC1), a cell surface proteoglycan, has gained interest for its role in tumor growth and as a potential biomarker. This study evaluated the efficacy of an ADC comprising a humanized anti-GPC1 monoclonal antibody with monomethyl auristatin E (GPC1-ADC) to target GPC1 in GC. Methods: GPC1 expression was assessed in GC cell lines and tissues. The cytotoxic efficacy of GPC1-ADC and its mechanism of action were evaluated using comprehensive in vitro assays. Further, in vivo efficacy was assessed in xenograft mouse models, focusing on tumor growth inhibition and its performance against peritoneal dissemination. Results: In vitro, GPC1-ADC exhibited significant cytotoxicity against GPC1-positive cell lines by inducing cell cycle arrest and apoptosis. Additionally, GPC1-ADC exhibited promising bystander-killing activity through cancer-associated fibroblasts, underscoring its potential to target the heterogeneous tumor cell microenvironment characteristics of GC. In vivo, GPC1-ADC significantly inhibited tumor growth, demonstrating a substantial therapeutic effect in a peritoneal dissemination model. Immunohistochemical analysis of tumor specimens from patients with GC revealed that 90.2% of differentiated types and 66.7% of poorly differentiated types exhibit high GPC1 expression. High GPC1 expression in tumor samples was significantly related to poorer clinical outcomes for progression-free and overall survival. Conclusions: GPC1-ADC exerts a direct antitumor effect on GPC1-positive GC cells. Additionally, GPC1-ADC can impact GPC1-negative cells via GPC1-positive stromal cells. This mechanism is likely owing to the characteristics of MMAE, which has a bystander effect as the payload of GPC1-ADC. Our results suggest that GPC1-ADC may be a potential therapeutic candidate for GPC1-positive GC. Citation Format: Yuji Suzuki, Satoshi Serada, Kota Kawabata, Tsuyoshi Takahashi, Yuichiro Doki, Tetsuji Naka. Assessing efficacy of anti-glypican-1antibody-drug conjugate as potential therapeutic approach for gastric 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 1559.
Abstract 3179: A comprehensive serial killing workflow for assessment of CAR T-cells
Authors: Xiaoyu Zhang, Jyothi Thyagabhavan Mony, Natalia Romero
Journal: Cancer Research (2025)

Abstract Adoptive cell therapy with chimeric antigen receptor T cells (CAR-T cells) has been highly successful in individuals with hematological malignancies. However, its efficacy against most solid tumors remains elusive due to short-term persistence and inadequate expansion of CAR T-cells within the tumor microenvironment. Traditional in vitro cytolysis assays often fail to reflect the true antitumor potential of the CAR T cells, as they typically involve brief co-culture periods and assess CAR T-cell performance only from a single perspective. To address these limitations, we developed a long-term multiplexed workflow that can robustly and comprehensively assess CAR T cell products. In our study, the EpCAM CAR T-cells were repeatedly challenged with an EpCAM expressing breast cancer cell line, T47D cells, over seven consecutive rounds. During each challenge, the EpCAM T-cells were directly added to the T47 D cells cultured on an E-Plate VIEW 96 (E-Plate) for 24 hours, at the effector to target ratio (E:T) of 0.5 :1. The CAR T-cell cytotoxicity against T47D cells was continuously measured over three days using an xCELLigence RTCA eSight system (eSight). After each co-culture round, the CAR T-cell metabolism, immunophenotype and percentage were evaluated using Agilent XF Pro analyzer and NovoCyte flow cytometer respectively. Following assessment, the challenged CAR T-cells were transferred to a new tumor cell-containing E-Plate to repeat the assay sequence. Our results indicate that: 1) although the percentage of CAR T-cells progressively increased from 25% to 80% by the fifth challenge round, a significant decline was observed in the sixth round; 2) CAR T-cells exhibited a gradual reduction in proliferation and cytotoxicity against tumor cells, along with an increase in the PD1+Tim3+ population across repeated challenges; and 3) CAR T-cells demonstrated a distinct metabolic profile, characterized by progressively decreased maximal respiration, spare respiratory capacity (SRC), and ATP production rate throughout the successive challenges. In conclusion, this multiplexed workflow enables comprehensive evaluation of CAR T-cell proliferation, killing potency, exhaustion phenotype, and metabolic profile over repeated tumor cell challenges, providing a more accurate prediction of their in vivo therapeutic efficacy. Citation Format: Xiaoyu Zhang, Jyothi Thyagabhavan Mony, Natalia Romero. A comprehensive serial killing workflow for assessment of CAR T-cells [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 3179.
Abstract 2131: Glycosylated protein targets open access to multiple tumor indications for different therapeutic modalities
Authors: Aaron C. Groen, Nisha Shrestha, Boris Klebanov, Hans H. Wandall
Journal: Cancer Research (2025)

Abstract Using advanced O-glycoproteomics we pinpointed relevant glycopeptide epitopes and developed a highly cancer-specific, humanized monoclonal antibody (R800). This antibody binds to truncated O-glycans in the context of a peptide backbone with low nanomolar affinity. The crystal structure of R800 provides insights into its binding specificity showing direct interaction with both peptide and the truncated glycan. Development of a companion diagnostic assay based on immunohistochemistry with the humanized therapeutic antibody confirmed the specificity of R800 across multiple epithelial cancers. This included selective binding to 20-30% of both primary and metastatic triple negative breast, lung, pancreatic, colorectal, and ovarian cancers. There was no binding to healthy tissues. The versatility of R800 allows the application of the mAb in multiple therapeutic modalities, including chimeric antigen receptor T-cell therapies (CAR-T cells) and antibody-drug conjugates (ADCs). In CAR-T cell applications using R800's antigen-binding domain demonstrated potent, selective cytotoxicity against R800-target expressing cancer cells in vitro in vivo in CDX models. In ADC applications, R800 formulated with either the anti-mitotic agent, monomethyl auristatin E payload (R800-MMAE) or with the topoisomerase 1 inhibitor payload, exatecan (R800- exatecan) show potent activity in vitro (EC50 ∼1nM) across multiple cell lines. Both R800 ADCs effectively eliminated tumors in preclinical PDX models, including lung, ovarian, and TN breast PDx models with a MED of 2mg/kg. By targeting the cancer-specific truncated O-glycans recognised by R800, we exploit a novel target space offering unparalleled cancer selectivity. This strategy holds significant potential for enhancing the efficacy and safety of treatments for solid tumors. Citation Format: Aaron C. Groen, Nisha Shrestha, Boris Klebanov, Constantine Theodoropulos Constantine Theodoropulos, Hans H. Wandall. Glycosylated protein targets open access to multiple tumor indications for different therapeutic modalities [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 2131.
Abstract 2827: Heat shock factor 1 regulates the cellular toxicity-induced autophagy in pancreatic ductal adenocarcinoma
Authors: Rejina Shrestha, Shruti Ghai, Ahmad Hegazi, Kuo-Hui Su
Journal: Cancer Research (2025)

Abstract Background: Heat shock factor 1 (HSF1) is a master transcriptional regulator of the proteotoxic stress response and has been known to be hyperactivated in pancreatic ductal adenocarcinoma (PDAC). Recent research has shown that ion-induced cellular toxicity (ferroptosis or cuproptosis) triggers autophagy—a critical mechanism that maintains cellular homeostasis. HSF1 has been established to mediate autophagy in a context-dependent manner. It has been reported that HSF1 prevents copper-induced toxicity in PDAC; however, it remains unclear whether HSF1 mediates autophagy as a mechanism of stress adaptation in response to aforementioned cellular toxicity. Objective: The objective of this study is to investigate the molecular mechanism of the role of HSF1 in cellular ion toxicity-induced autophagy. Methods: Human PDAC cell line MIA PaCa-2 was used for this study. A CellTiter Blue Cell Viability Assay was used to determine the IC50 of Erastin, a well-known ferroptosis inducer, and Elesclomol/copper, a copper ionophore, in human PDAC cells. An HSF1 overexpressed (HSF1_WT) MIA PaCa-2 cell was used to test ion-induced toxicity in comparison to the control (LacZ) MIA PaCa-2 cells. Western blotting was used to detect the protein HSF1, autophagy markers, and internal loading control. Results: In human MIA PaCa-2 cells, Elesclemol/copper and Erastin induced cell death. Elesclomol/copper and Erastin induced increased autophagy marker microtubule-associated protein 1A/1B-light chain 3β (LC3β) lipidation and decreased the expression of total HSF1 protein in a dose-dependent manner. The overexpression of HSF1 prevented the Erastin-induced LC3β lipidation. Conclusion: HSF1 plays a role in the induction of autophagy, which functions as a stress-adaptive mechanism in the tumor cell in response to the toxicities induced by ferroptosis and cuproptosis inducers. Citation Format: Rejina Shrestha, Shruti Ghai, Ahmad Hegazi, Kuo-Hui Su. Heat shock factor 1 regulates the cellular toxicity-induced autophagy 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 2827.
Abstract 2393: Gene regulatory networks of enzalutamide resistance in prostate cancer
Authors: Sini Hakkola, Anni Perämäki, Karishma Sajnani, Antti Kiviaho, Alfonso Urbanucci, Matti Nykter, Mikael Marttinen
Journal: Cancer Research (2025)

Abstract Introduction: Castration-resistant prostate cancer (CPRC) is typically managed with antiandrogens, such as enzalutamide (ENZA), which can delay disease progression but are not curative, as resistance to these treatments eventually develops. This resistance is likely a consequence of significant remodeling of gene regulatory landscape of cells adapting to an androgen-deprived, stressful environment. Understanding the aberrancies in gene regulation underlying ENZA resistance is essential for improving the therapeutic strategies for CRPC. Methods: Using single-cell chromatin accessibility (ATAC) and transcriptome sequencing data sourced from the parental and ENZA-resistant LNCaP prostate cancer cells, we have applied knowledge graph-based neural networks to model transcription factor (TF) regulons and their associated molecular processes underlying the cell states from initial ENZA response towards ENZA resistance. Results: We have identified TF regulons associated with stress responses, cell cycle progression and androgen signaling, altered in ENZA-resistant cells. Specifically, the ENZA-resistant cells are characterized by the gain of SOX4 regulon, likely to contribute to the metabolic and proliferative reprogramming of the resistant cells. Cell cycle analysis revealed that while the cell proportion is largest in G1 phase in each treatment, the proportion of cells in S phase is increased in resistant samples, suggesting enhanced S-phase transition in resistant cells in contrast to G1 arrest caused by ENZA in treatment-responsive cells. We validate our findings in independent transcriptomic studies of ENZA-resistant VCaP and DuCaP cell lines indicating the robustness of the results. Moreover, utilizing spatial transcriptomic data from a longitudinal patient cohort, we pinpoint that the SOX4 regulon target genes are enriched in the epithelium of CRPC patients, compared to treatment-naïve and neoadjuvant-treated disease states. Conclusion: In summary, we determine gene regulatory alterations associated with ENZA resistance in preclinical models, providing valuable insights into uncovering the mechanisms of resistance to antiandrogens in CRPC. Citation Format: Sini Hakkola, Anni Perämäki, Karishma Sajnani, Antti Kiviaho, Alfonso Urbanucci, Matti Nykter, Mikael Marttinen. Gene regulatory networks of enzalutamide resistance 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 2393.
Abstract 2395: The role of exonized mobile elements in chimeric transcript emergence in glioblastoma
Authors: Rafael L. Mercuri, Thiago L. Miller, Filipe F. dos Santos, Matheus de Lima, Aline Rangel-Pozzo, Pedro A. Galante
Journal: Cancer Research (2025)

Abstract Background: Glioblastoma (GBM) is the most aggressive type of primary brain tumor in adults, with a median survival of approximately 15 months. Unfortunately, the prognosis for GBM has remained unfavorable for decades. The genetic and transcriptomic heterogeneity of GBM complicates treatment, underscoring the need for a more comprehensive understanding of its molecular basis. Recently, retrotransposons have been shown to influence gene expression and the formation of chimeric transcripts. Although they are associated with various cancers, their precise role in GBM remains unclear. In this study, using paired-end RNA-Seq data from The Cancer Genome Atlas (TCGA) and the GBM (U251) cell line, we examined the exonization of mobile elements and the generation of GBM-specific chimeric transcripts. For retroelement references, we utilized RepeatMasker annotations. To detect, characterize, and quantify the expression of chimeric transcripts, we developed FREDY, a tool designed to identify the exonization of retrotransposable elements in RNA-seq data. Initially, we identified 1, 012 chimeric transcripts linked to the exonization of intragenic (intronic) mobile elements. Specifically, Alu element exonization was the most common (∼45%) and occurred primarily in the 5' regions of transcripts. As expected, the majority (83%) of these exonizations involved Alu elements located in the opposite transcriptional direction of their host genes. In contrast, LINE1 elements and retrocopies of protein-coding genes were predominantly exonized (46% and 56.7%, respectively) in the 3' regions of host genes and in the same transcriptional direction as their host genes. Notably, we identified two candidate chimeric transcripts impacting the tumor suppressor gene ROS1. Furthermore, when comparing potential protein domains, we found that the coding sequences of these chimeric transcripts lacked two ROS1 domains, suggesting a premature cessation of transcription and potentially translation. Additionally, we quantified that these chimeric transcripts represent 84% of the total expression of the ROS1 gene in the identified GBM samples. Conclusions: We have established a framework for detecting chimeric transcript formation in cancer through the exonization of mobile elements. We applied this approach to GBM samples and cell lines, identifying chimeric transcripts of the tumor suppressor gene ROS1 that may play a significant role in GBM carcinogenesis. Sponsor: FAPESP 20/02413-4 Citation Format: Rafael L. Mercuri, Thiago L. Miller, Filipe F. dos Santos, Matheus de Lima, Aline Rangel-Pozzo, Pedro A. Galante. The role of exonized mobile elements in chimeric transcript emergence 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 2395.
Abstract 281: Plasma metabolomic profiling identifies novel biomarkers for gastric cancer diagnosis and prognosis
Authors: Zun Li, Xiangnan Zhang, Yanxin Yao, Yubei Huang, Zhangyan Lv, Hongji Dai, Kexin Chen, Ben Liu
Journal: Cancer Research (2025)

Abstract Gastric cancer (GC) remains a significant global health challenge, representing the fifth leading cause of cancer-related mortality. Altered metabolism plays a crucial role in GC development and progression. This study aimed to identify plasma metabolic biomarkers for improved GC diagnosis and prognosis prediction. We performed untargeted metabolomic profiling of plasma samples from 105 GC patients and 120 healthy controls using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Following rigorous quality control, orthogonal partial least squares discriminant analysis (OPLS-DA) identified 562 differentially abundant metabolites between groups. Pathway enrichment analysis revealed significant alterations in metabolic pathways associated with amino acid metabolism, lipid metabolism, and hormone signaling. Machine learning algorithms were employed to develop diagnostic and prognostic models based on these differentially abundant metabolites. A four-metabolite diagnostic model achieved high sensitivity (0.86) and specificity (0.95) in an independent validation cohort, significantly outperforming conventional protein-based diagnostic markers. Furthermore, our prognostic model demonstrated superior performance compared to established clinical parameters, effectively stratifying patients into distinct risk groups for personalized therapeutic strategies. This comprehensive metabolomic analysis provides novel insights into the metabolic landscape of GC and identifies promising biomarkers for improved clinical management. Citation Format: Zun Li, Xiangnan Zhang, Yanxin Yao, Yubei Huang, Zhangyan Lv, Hongji Dai, Kexin Chen, Ben Liu. Plasma metabolomic profiling identifies novel biomarkers for gastric cancer diagnosis and prognosis [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 281.