tbuckley/cabot-search huggingface dataset:
Abstract 4961: Bridging gaps in cervical cancer screening: Prevalence and key predictors among women aged 25-59 years in Eswatini
Authors: Abenezer M. Tafese, Bikiltu D. Dirbaba, Meseker T. Fentie, Charnita Zeigler-Johnson
Journal: Cancer Research (2025)

Abstract Background: Cervical cancer is the most prevalent cancer and the leading cause of cancer-related deaths among women in Eswatini, which reported the world’s highest cervical cancer incidence (95.9 per 100,000) and mortality (64.3 per 100,000) rates in 2022. Despite this significant burden, cervical cancer screening coverage was limited to 19% as per WHO’s 2019 report. This study assessed progress in cervical cancer screening prevalence and identified predictors of screening uptake among women aged 25-59 in Eswatini. Method: Data were obtained from the 2021 Eswatini Population-based HIV Impact Assessment Survey, a cross-sectional household survey designed to assess the coverage and impact of HIV services among individuals aged 15 years and older. In this study, women aged 25-59, the national target group for cervical cancer screening, were included. Survey weights were applied to adjust for the study design. Bivariate analyses identified factors associated with screening uptake, with significant variables (p &amp;lt; 0.05) entered into multivariate logistic regression models. Screening predictors were identified using stepwise backward elimination, with results reported as adjusted odds ratios (OR) and 95% confidence intervals (CI). Result: Among 3,193 women aged 25-59, the lifetime cervical cancer screening prevalence was 48.2%. HIV-positive women had significantly higher odds of screening compared to HIV-negative women (59% vs. 39%; OR=2.22, 95%CI:1.90-2.59). Women aged 36-45 were more likely to undergo screening than those aged 25-35 (OR=1.35, 95%CI: 1.12-1.62). Higher economic status (fourth vs. lowest wealth quintile) was associated with increased screening uptake (OR=1.41, 95% CI: 1.06-1.88). Conversely, lower odds of screening were observed among women with no formal education (OR=0.58, 95%CI: 0.41-0.84), no healthcare visits in the past 12 months (OR=0.67, 95% CI: 0.55-0.83), and no use of family planning services (OR=0.81, 95% CI: 0.68-0.96). Women with no sexual partners were also less likely to be screened compared to those with two or more partners (OR=0.08, 95% CI: 0.01-0.62). Although rural women had lower odds of screening than urban women, the difference was not statistically significant (OR=0.86, 95% CI: 0.70-1.05). Conclusion: While cervical cancer screening in Eswatini has shown significant progress, disparities persist among women with lower socioeconomic status, limited education, and fewer healthcare visits. Citation Format: Abenezer M. Tafese, Bikiltu D. Dirbaba, Meseker T. Fentie, Charnita Zeigler-Johnson. Bridging gaps in cervical cancer screening: Prevalence and key predictors among women aged 25-59 years in Eswatini [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 4961.
Abstract 5475: Leveraging LC-MS workflows to characterize a novel WRN covalent inhibitor
Authors: Kurt Baltier, Anthony Tubbs, Doug McLaughlin, Giulia Bottoni, Allison Drew, Brian Erickson, Craig Braun
Journal: Cancer Research (2025)

Werner protein (WRN) is a helicase with functions critical to DNA repair pathways, and as such is an active target for the development of cancer therapeutics. Notably, WRN has been demonstrated as a synthetic lethality target in DNA mismatch repair deficient (dMMR)/microsatellite instable (MSI-H) tumors owing to its role in the DNA damage response. Accordingly, the development of small-molecule WRN inhibitors is an active and attractive area of cancer research and has the potential to be a powerful new therapeutic modality in several cancers including colorectal, gastric, and endometrial. Here, we report the application of targeted and discovery LC-MS workflows towards the characterization of M6021, a small molecule covalent inhibitor of WRN. A custom targeted LC-MS assay has been developed and optimized for detection and quantification of covalent compound engagement to WRN in preclinical models, including several cancer cell lines and mouse xenograft models. This assay enables reproducible, precise and accurate quantitative characterization of near-complete WRN engagement in clinically relevant biological matrices, despite low endogenous WRN expression and treatment-induced reduction in WRN levels. Plate-based sample preparation and analysis enables high-throughput evaluation of multiple experimental parameters (dose, treatment time, matrix, etc) across meaningful cohorts of replicates. Further, we employed a discovery LC-MS based covalent inhibitor selectivity assay to demonstrate that M6021 is highly selective for WRN, proteome-wide. Using this assay, we demonstrate that the novel WRN inhibitor M6021 is a potent and selective covalent inhibitor of WRN helicase, suitable for use as a high-quality chemical probe for understanding WRN biology in dMMR/MSI-H tumors. Citation Format: Kurt Baltier, Anthony Tubbs, Doug McLaughlin, Giulia Bottoni, Allison Drew, Brian Erickson, Craig Braun. Leveraging LC-MS workflows to characterize a novel WRN covalent inhibitor [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 5475.
Abstract 5454: DB-1325, a BCMA-targeting antibody-drug conjugate with a Duality Unique Payload, exhibits promising efficacy and safety in preclinical multiple myeloma treatment
Authors: Shengchao Lin, Bing Li, Yu Zhang, Jun Yao, Rong Shi, Yang Qiu, Haiqing Hua
Journal: Cancer Research (2025)

Introduction: B cell maturation antigen (BCMA) overexpression has been found on the surface of the malignant plasma cells in the bone marrow of multiple myeloma (MM) patients. In recent years, innovative medicines targeting BCMA such as antibody-drug conjugates (ADC), T-cell engager and CAR-T have made great progress in the treatment of MM patients. Among them, belantamab mafodotin has been approved by FDA. However, a significant fraction of patients does not respond, or respond for a short period of time, to belantamab mafodotin. Thus, there remains unmet medical needs for BCMA-targeting ADC with novel mode of actions. DB-1325 is a novel BCMA-targeting ADC comprised of belantamab and PDUP5, a Duality Unique Payload (DUP) inhibiting mRNA translation, conjugated through a cleavable linker. Methods: A proprietary inhibitor of mRNA translation PDUP5 was discovery through a campaign of medicinal chemical design and screening. A cleavable linker was designed to be attached to PDUP5, resulting in LPDUP5. Belantamab was conjugated with LPDUP5 to yield DB-1325. The therapeutic profile of DB-1325, including in vitro and in vivo efficacy, and its safety profile was assessed in preclinical models. Results: PDUP5 exhibited sub-nanomolar to nanomolar potency in in vitro cell killing test on various MM cell lines. DB-1325 (belantamab-LPDUP5) showed robust in vitro anti-proliferation activity in multiple BCMA-expressing cell models (e.g. NCI-H929, KMS-11, MM1S, MOLP8) with activity similar to belantamab mafodotin. In addition, we observed robust efficacy of DB-1325 in several in vivo xenograft models following a single dose treatment. In NCI-H929 CDX model, treatment with DB1325 demonstrated anti-tumor activity superior to belantamab mafodotin when given at an equivalent dose. Furthermore, DB-1325 was well-tolerated at a preliminary toxicology assessment using monkeys, with favorable toxicokinetic profile. Conclusions: DB-1325 is a novel and promising therapy for MM and currently in preclinical development as a first-in-class ADC with mRNA translation inhibitions as its major mode of action. Citation Format: Shengchao Lin, Bing Li, Yu Zhang, Jun Yao, Rong Shi, Yang Qiu, Haiqing Hua. DB-1325, a BCMA-targeting antibody-drug conjugate with a Duality Unique Payload, exhibits promising efficacy and safety in preclinical multiple myeloma treatment [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 5454.
Abstract 6959: CK2 inhibition exhibits synergistic effect with KIT inhibitors in acute lymphoblastic leukemia
Authors: Katarina Dovat, Daniel Bogush, Julia Randazzo, Marjon Rafie, Stephanie Buczkowski, Rabab Husain, Joseph Schramm, Yali Ding, Chingakham Singh, Dhimant Desai
Journal: Cancer Research (2025)

Abstract Survival for pre-B cell Acute lymphoblastic leukemia (B-ALL) has significantly improved, but High Risk (HR) subgroups continue to result in increased death for pediatric oncology patients. Novel treatment strategies are required to conquer chemotherapy resistance and improve life expectancy for HR B-ALL. Deletion of IKZF1, resulting in decreased IKAROS function, is a feature of high-risk B-ALL that is associated with resistance to chemotherapy and a poor prognosis. Casein kinase 2 (CK2) is a protein kinase upregulated in B-ALL, which phosphorylates IKAROS and reduces Ikaros DNA binding affinity. This results in a loss of IKAROS-mediated transcriptional regulation in B-ALL patients. Previous studies have shown that pharmacologic inhibition of CK2 with CX-4945 recovers IKAROS function as a transcriptional regulator. Receptor tyrosine kinase c-KIT is transcriptionally regulated by IKAROS and is often upregulated in B-ALL. The purpose of this study was to determine whether restoration of IKAROS function as c-KIT repressor via CX-4945 would act in a synergistic manner with c-KIT inhibitor imatinib in B-ALL. B-ALL cells were treated with imatinib over 72-hours to demonstrate the half-maximal inhibitory concentration (IC50). The IC50 was used to determine the range of the concentration of imatinib to be used in association with CX-4945 in a 72-hour synergy analysis of cytotoxicity. Cell viability was determined using WST-1 cell proliferation assay. The data was analyzed using Calcusyn and synergy was specified as a combination index below 0.85. The study was repeated with several different drug concentrations to establish a more precise range of synergy. The cytotoxicity of single drug c-KIT inhibitor, Imatinib, in Nalm6 B-ALL produced an IC50 of 25uM while CK2 inhibitor CX-4945 has IC50 of 4uM. When a combination was administered with a constant dose of CX-4945 at 4uM and different concentrations of imatinib, synergy was detected at several dose combinations. In conclusion, our results demonstrate that CK2 inhibitor, CX-4945, and c-KIT inhibitor, imatinib, exhibit a synergistic therapeutic effect on B-ALL cells. Presented data provide a rational for the use of combination therapy with CK2 inhibitors and imatinib for treatment of high-risk B-ALL, including Philadelphia positive (Ph+) B-ALL. Citation Format: Katarina Dovat, Daniel Bogush, Julia Randazzo, Marjon Rafie, Stephanie Buczkowski, Rabab Husain, Joseph Schramm, Yali Ding, Chingakham Singh, Dhimant Desai. CK2 inhibition exhibits synergistic effect with KIT inhibitors in acute lymphoblastic leukemia [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 6959.
Abstract 2100: Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical-outcomes in small cell lung cancer
Authors: Chaoqiang Deng, Changbin Zhu, Tao Hu, Jing Wang, Haiquan Chen
Journal: Cancer Research (2025)

Abstract Recent advances have shed light on the molecular heterogeneity of small cell lung cancer (SCLC), yet the spatial organizations and cellular interactions in tumor immune microenvironment remain to be elucidated. Here, we employed co-detection by indexing (CODEX) and multi-omics profiling to delineate the spatial landscape for 165 SCLC patients, generating 267 high-dimensional images encompassing over 9.3 million cells. Integrating CODEX and genomic data revealed a multi-positive tumor cell neighborhood within ASCL1+ (SCLC-A) subtype, characterized by high SLFN11 expression and associated with poor prognosis. We further developed a cell colony detection algorithm (ColonyMap) and revealed a spatially assembled immune niche consisting of antitumoral macrophages, CD8+ T cells and natural killer T cells (MT2) which highly correlated with superior survival, and predicted improving immunotherapy response in an independent cohort. This study serves as a valuable resource to study SCLC spatial heterogeneity and offers insights into potential patient stratification and personalized treatments. Citation Format: Chaoqiang Deng, Changbin Zhu, Tao Hu, Jing Wang, Haiquan Chen. Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical-outcomes in small cell lung 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 2100.
Abstract 2132: KA-3123-LD38: a novel bispecific antibody-drug conjugate (ADC) targeting EGFR and B7H3 with a DNA topoisomerase I inhibitor payload
Authors: Guojin Wu, Chuanying Xu, Weihong Nian, Zhengcheng Guo, Jiabei Liang, Feng He, Qing Zhou
Journal: Cancer Research (2025)

Abstract KA-3123-LD38 is a novel bispecific antibody-drug conjugate (ADC) designed to target both EGFR and B7H3, two markers that are highly expressed in various tumor cells but have limited expression in normal tissues. The co-expression of EGFR and B7H3 in tumor cells is particularly high, making them promising therapeutic targets. By targeting both of these markers simultaneously, KA-3123-LD38 aims to reduce the risk of "on-target/off-tumor" cytotoxicity, a common side effect in cancer therapies. This ADC is a IgG1 with a common light chain, conjugated with LD-38, an Escugen proprietary ADC platform composed of TopIi payload and highly hydrophilic stable cleavable linker. KA-3123-LD38 binds to B7H3 with high affinity, with a Kd of less than 0.01 nM, while its affinity for EGFR is weaker, with a Kd greater than 10 nM. When compared to monoclonal antibodies targeting B7H3, KA-3123-LD38 exhibits a significantly faster internalization rate in tumor cells that co-express EGFR and B7H3. In vitro assays show that KA-3123-LD38 effectively induces cytotoxicity in tumor cells expressing either EGFR and B7H3 together or B7H3 alone. However, the cytotoxic effect is notably stronger in cells co-expressing both targets. Furthermore, KA-3123-LD38 demonstrates strong bystander killing activity, further enhancing its therapeutic potential. In xenograft mouse models, KA-3123-LD38 strongly inhibits the growth of a variety of tumor types, including NSCLC, esophageal squamous cell carcinoma, colorectal cancer, and gastric cancer. Ongoing toxicity studies suggest that KA-3123-LD38 has a favorable safety profile, with low toxicity observed. These promising results highlight KA-3123-LD38 as a potentially powerful treatment for a broad range of solid tumors. Citation Format: Guojin Wu, Chuanying Xu, Weihong Nian, Zhengcheng Guo, Jiabei Liang, Feng He, Qing Zhou. KA-3123-LD38: a novel bispecific antibody-drug conjugate (ADC) targeting EGFR and B7H3 with a DNA topoisomerase I inhibitor payload [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 2132.
Abstract 5786: Rapidly assess sentinel lymph node metastasis status in breast cancer by a near-infrared fluorescent probe targeting CK
Authors: Junhong Chen, Wei-Ling Chen, Yuan-Yuan Zhu Zhu, Zhao Wu, Ting-wen Guo, Guo-Jun Zhang
Journal: Cancer Research (2025)

Abstract Purpose: At present, surgery is still a main treatment method for breast malignant tumors, but the problems of edema and tumor recurrence faced by patients after surgeries are still relatively common. The main reason for this is closely related to the resection of metastatic sentinel lymph node (SLN) during surgery. The method of identifying SLN by methylene blue (MB) and technetium 99m tracing is not clearly targeted and can’t judge the metastatic status of SLNs. Therefore, there is an urgent need to develop tracers that specifically identify the metastatic status of SLN. Our team successfully synthesized ICG-CK, a fluorescent molecular probe targeting pan-CK. Through animal experiments, we found that the probe can identify the metastatic status of SLN in vivo and ex vivo. Methods: 1. The penetration and characteristics of the ICG-CK were evaluated. 2. The ability of ICG-CK to recognize different breast cancer cell lines was verified by cell uptake experiments. 3. The ability of ICG-CK to identify the metastatic status of SLN was verified by in vivo imaging experiments. 4. The ability of ICG-CK to identify the metastatic status of ex vivo SLN was verified by co-incubation with ex vivo tissue. Results: 1. The ICG-CK probe was successfully synthesized, with good stability, biocompatibility and strong NIR-II fluorescence emission ability. 2. ICG-CK could specifically target 4T1 cell which with high CK expression compared with ICG-IgG, and there was a statistically significant difference between the two, p&amp;lt;0.0001. 3. In vivo imaging experiments, the fluorescence imaging of tumor-bearing mice showed that ICG-CK was easily drained to SLN and targeted to identify metastatic 4T1 tumor cells, producing a strong fluorescent signal, and the SBR of metastatic SLN and normal SLN was 3.34, p&amp;lt;0.05. 4. By imaging isolated SLN from tumor-bearing mice, we found that after co-incubation with ICG-CK of isolated SLN, isolated SLN produced a strong fluorescent signal that was significantly different from normal SLN, p&amp;lt;0.01. Summary: Our results show that ICG-CK has a strong ability to identify metastatic SLN compared with normal SLN in breast cancer, both in vivo and ex vivo imaging experiments, and it can produce a strong fluorescence signal in the near-infrared second region. Therefore, our study provides a basis for further exploration of the use of ICG-CK to assess the metastatic status of SLN in real-time intraoperatively. Citation Format: Junhong Chen, Wei-Ling Chen, Yuan-Yuan Zhu Zhu, Zhao Wu, Ting-wen Guo, Guo-Jun Zhang. Rapidly assess sentinel lymph node metastasis status in breast cancer by a near-infrared fluorescent probe targeting CK [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 5786.
Abstract 2094: Development of a multiomic workflow using Oncore Pro X to stain tissues for high performance Dual Channel™ Validation of RNA expression with downstream quantitation using AI-based image analysis with Oncotopix Discovery™
Authors: Randy Chen, Aneesh Acharya, Daniel Winkowski, Jason Ramos, Harry Choi, Regan Baird
Journal: Cancer Research (2025)

Abstract Accurate quantification of RNA expression remains a critical challenge in advancing RNA-ISH multiomic technologies for translational and clinical applications. Current barriers include lack of guidelines for assay validation and difficulties in correlating RNA abundance with spatial localization. In this study, we introduce a robust pipeline leveraging Dual Channel™ Validation (DCV) of HCR™ HiFi Probes and AI-enabled analysis to enable relative quantification of RNA abundance. The DCV approach uses two spectrally distinct fluorescent channels to confirm the specificity and sensitivity of RNA detection. This dual-channel strategy minimizes false positives while providing a reliable proxy for RNA transcript abundance through fluorescent intensity correlations. To enhance RNA quantitation, our pipeline integrates automated tissue staining for consistent and high-quality labeling plus advanced AI-based algorithms trained on combined cellular nuclear plus membrane segmentation markers to precisely delineate cell boundaries. This dual-marker framework addresses limitations of rule based nuclear expansion-based segmentation methods and improves the accuracy of RNA spot assignment. Our results demonstrate that DCV, combined with autostaining and AI-enabled cellular segmentation, achieves superior quantification fidelity. This approach not only validates RNA-ISH assay performance but also provides a scalable, reproducible method for relative RNA quantitation across diverse tissue types. By coupling high-performance probes with optimized automated tissue staining (on Oncore Pro X) and advanced computational analysis, our pipeline bridges critical gaps in RNA quantification, facilitating reliable, clinically meaningful insights into RNA expression within complex tissue environments. Citation Format: Randy Chen, Aneesh Acharya, Daniel Winkowski, Jason Ramos, Harry Choi, Regan Baird. Development of a multiomic workflow using Oncore Pro X to stain tissues for high performance Dual Channel™ Validation of RNA expression with downstream quantitation using AI-based image analysis with Oncotopix Discovery™ [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 2094.
The Rise of Psilocybin Use in the United States: A Multisource Observational Study
Authors: Karilynn M. Rockhill, Joshua C. Black, Michael S. Ladka, Kanku B. Sumbundu, Heather A. Olsen, Jennifer S. Jewell, Joshua Hunt, R. Cameron Wolf, Karuna Nerurkar, Richard C. Dart, Andrew A. Monte
Journal: Annals of Internal Medicine (2025)