tbuckley/cabot-search huggingface dataset:
Abstract 4002: Development of an organoid coculture model to investigate tumor immune interactions and therapeutic strategies in prostate cancer
Authors: Kinjal Bhadresha, Jessica L. Horner, Jessica D. Kindrick, Douglas K. Price, Cindy H. Chau, William D. Figg
Journal: Cancer Research (2025)

While immunotherapy has demonstrated remarkable success in other malignancies, its efficacy in prostate cancer remains limited. Organoid models, capable of recapitulating patient-specific therapeutic responses, offer a promising platform for studying tumor biology and treatment responses. However, their utility in modeling immune interactions remains underdeveloped. To address this, we established an in vitro co-culture system of tumor organoids and immune cells to investigate tumor-immune interactions and identify novel therapeutic targets for aggressive prostate cancer. Using publicly available LuCaP PDX microarray datasets (GSE199596 and GSE113743), we identified the downregulation of antigen processing and presentation (APP) pathways, indicative of immune evasion mechanisms. Moreover, our analysis revealed overexpression of macrophage-polarizing factors, such as the STAT signaling pathway, ARG1, and MALAT1, which are implicated in tumor progression, metastasis, and drug resistance. To experimentally validate these findings, we developed and optimized a macrophage co-culture model utilizing organoids derived from LuCaP167 and LuCaP167CR, effectively recapitulating distinct tumor microenvironment characteristics associated with castration resistance. We further assessed for drug response using targeted and Immunotherapeutics within this system to evaluate their therapeutic potential. This proof-of-concept study highlights the potential of this sustainable and scalable co-culture platform for studying cancer-immune interactions ex vivo. The model serves as a valuable tool for evaluating the efficacy of existing therapeutics and discovering novel agents that enhance immune responses in advanced prostate cancer. Citation Format: Kinjal Bhadresha, Jessica L. Horner, Jessica D. Kindrick, Douglas K. Price, Cindy H. Chau, William D. Figg. Development of an organoid coculture model to investigate tumor immune interactions and therapeutic strategies 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 4002.
Abstract 6885: Plectin as a novel therapeutic target for pancreatic cancer
Authors: Cody L. Wolf, Roxanne K. Ruiz, Julien Dimastromatteo, Samantha Perez, Matthew J. Reilley, Kimberly A. Kelly
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the 3rd deadliest cancer in the United States with only a 5-year survival rate of 13%, demonstrating a desperate need for novel therapeutic targets to significantly enhance options for patients. In 2008, Kelly et al. pioneered a phage-display-based functional-proteomic approach and identified a cytolinker protein, plectin, which was mislocalized and ubiquitously expressed on the membrane of PDAC. This unique localization of plectin, called cell surface plectin (CSP), has since been found to be expressed on the cell surface of many cancer subtypes, including PDAC, ovarian carcinoma and cholangiocarcinoma, but remains cytoplasmic in normal tissues. Knockdown of plectin and an anti-CSP functional monoclonal antibody revealed the importance of CSP to proliferation, migration, and invasion in cancers. Recently, a phase 1 clinical trial using an anti-CSP antibody, ZB131 (NCT05074472) in CSP positive cancer subtypes showed ZB131 as a viable and safe drug candidate for treatment. In the trial, treatment with ZB31 led to stable disease in 3 out of 9 PDAC patients. In order to more fully understand the mechanism of action of ZB131 and to obtain comprehensive understanding of molecular signaling of CSP in cancer we have employed bioinformatic strategies as well as knock outs using CRISPR/Cas9 inducible systems. Transcriptomic data from bulk and single cell RNA-seq data from human PDAC revealed that CSP overexpressing tumors were enriched for integrin-extracellular matrix interactions, suggesting CSP plays a major role in matrix remodeling and metastasis. Additionally, treatment with anti-CSP antibody led to a decrease in classic signaling cascades associated with cancer progression such as SRC, PRAS40, STAT3, AKT, and ERK1/2. The cumulative work from this research highlights the role of CSP in PDAC and suggests a desperate need for an anti-CSP therapeutic for patients. Citation Format: Cody L. Wolf, Roxanne K. Ruiz, Julien Dimastromatteo, Samantha Perez, Matthew J. Reilley, Kimberly A. Kelly. Plectin as a novel therapeutic target for pancreatic 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 6885.
Abstract 5209: Sequential orthogonal assays for longitudinal and endpoint characterization of three-dimensional cell and tissue culture models
Authors: Olivier De Wever, Eva Blondeel
Journal: Cancer Research (2025)

Spheroids are near-spherical reaggregated multicellular three-dimensional (3D) structures generated from cells or cell cultures from healthy as well as pathological tissue. Basic and translational spheroid application across academia and industry led to the development of multiple set-ups and analysis methods which mostly lack the modularity to maximally phenotype spheroids. This protocol presents the self-assembly of single-cell suspensions into spheroids by the liquid overlay method followed by a modular framework for a multifaceted phenotyping of spheroids. Cell seeding, supernatant handling, and compound administration are elaborated by both manual and automated procedures. The phenotyping modules contain a suite of orthogonal assays to analyze spheroids longitudinally and/or at an endpoint. Longitudinal analyses include morphometry with/out spheroid or cell state specific information, and supernatant evaluation (nutrient consumption and metabolite/cytokine production). Spheroids can also be used as starting point to monitor single and collective cell migration and invasion. At an endpoint, spheroids are lysed, fixed, or dissociated into single cells. Endpoint analyses allow to investigate molecular content, single-cell composition and state, and architecture with spatial cell and subcellular specific information. Each module addresses time requirements and quality control indicators to support reproducibility. The presented complementary techniques can be readily adopted by researchers experienced in cell culture and basic molecular biology. We anticipate that this modular protocol will advance the application of 3D biology by providing scalable and complementary methods. Citation Format: Olivier De Wever, Eva Blondeel. Sequential orthogonal assays for longitudinal and endpoint characterization of three-dimensional cell and tissue culture models [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 5209.
Abstract 5672: Detecting tissue susceptibility to celecoxib treatment using a whole-body imaging approach
Authors: Steven Johnson, Justin Jeffery, Jungwha Lee, Ming Zhao
Journal: Cancer Research (2025)

Abstract Purpose: The goal of this study was to evaluate an in vivo imaging technique, which detects phospholipid membrane reorganization, as a molecular marker for tissue response induced by celecoxib as a canonical black box drug which is also being repurposed for anticancer treatment. Methods: 99mTc-duramycin was used as a phosphatidylethanolamine (PE)-binding imaging agent and was injected intravenously at 1 hour prior to imaging at designated time points. Sprague Dawley rats (male, 8-10 weeks) were treated with a single dose of 200 mg/kg or 1000 mg/kg celecoxib via oral gavage. A pilot study was conducted in duplicates with planar imaging on days 1, 3, 5 and 7 to determine the approximate window of signal changes, then whole-body single photon emission computed tomography (SPECT) was acquired for nontreated control, 200 mg/kg and 1000 mg/kg celecoxib-treated groups (n=12 per group). Blood and tissues from 4 animals in each group were collected for complete blood and serum panels and histopathology. The radioactivity uptake in tissues and organs were determined and statistically compared to the control group using unpaired t test. Results: The imaging data detected no significant changes with low dose (200 mg/kg) celecoxib treatment, but in a number of tissues/organs in high dose (1000 mg/kg) treatment, including the adipose tissue, blood, brain, upper right quadrant of the abdomen, heart, kidney, skeletal muscle, stomach, and testes. Histopathology analysis is ongoing to validate the imaging findings. Data from complete serum panel detected significantly elevated total protein, albumin and sodium. Conclusion: The study demonstrated the assessment of tissue susceptibility as a result of celecoxib treatment, which were consistent with known adverse effects of the drug. The current approach will be useful for detecting potential off-target side effects of anticancer treatments and drug candidates. Citation Format: Steven Johnson, Justin Jeffery, Jungwha Lee, Ming Zhao. Detecting tissue susceptibility to celecoxib treatment using a whole-body imaging approach [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 5672.
Abstract 4501: Temporal Validation of Novel Therapeutic Targets in Non-Hodgkin Lymphoma
Authors: Tudor I. Oprea, Mohammed Quazi, Suman Sirimulla, Cristian G. Bologa, Ruben Karapetian, Alexey Pushechnikov, Bill Farley, Nikolay Savchuk
Journal: Cancer Research (2025)

Abstract In 2024, we reported the development of knowledge graph machine learning (KGML) models focused on 41 blood cancers (1), using several public resources. Our disclosure identified 19 drug targets that are likely to be druggable and fall into the "Tchem" category—that is, targets perturbed by small molecules (2). These 19 genes had limited or no known blood cancer associations, when evaluated via the DISEASES platform (3). Upon re-evaluation a year later, five genes (BLK, FCER2, FRK, CAMK2D, and EPHB1) were no longer investigated due to a growing body of literature. Of the remaining 14 genes (see Table 1), only two (IRAK3 and ITPKB) have marginally relevant associations with lymphoma, leukemia, or myeloma, according to the DISEASES platform (3). Table 1 summarizes cytotoxicity assays for the 14 targets, using compounds specific for each target. Non-Hodgkin lymphoma cell lines were: Toledo (CL1), SU-DHL-6 (CL2), TMD8 (CL3), and JeKo-1 (CL4). CC50 (50% cytotoxic concentration) values, measured in micromolar concentrations, were collected at 3 (_3d) and 7 days (_7d), respectively; "nd" - not determined; "gt" - greater than value. Except for GRM8, all targets exhibited at least one micromolar CC50 value. Five kinases (IRAK3, ITPKB, PRKCE, ACVR2B, and PIM1), one enzyme (ADCY1), and one ion channel (TRPV4) have at least one sub-micromolar CC50 value (25 values total). Some targets (e.g., GPR18, a G-protein coupled receptor; and ITPKB, a kinase) show low micromolar CC50s at 7 days, with gt 20 CC50 after 3 days, suggesting target engagement. Confirmatory target engagement experiments are in progress. Although preliminary, these data validate our KGML approach (1), as they implicate at least seven targets in non-Hodgkin lymphoma disease biology, with potentially novel therapeutic applications. References 1. Quazi M, et al. Cancer Res (2024) 84 (6_Supplement): 3535. 2. Oprea TI, et al. Nat Rev Drug Discov. (2018) 17:317-32. 3. Grissa D, et al. Database (2022) baac019. Citation Format: Tudor I. Oprea, Mohammed Quazi, Suman Sirimulla, Cristian G. Bologa, Ruben Karapetian, Alexey Pushechnikov, Bill Farley, Nikolay Savchuk. Temporal Validation of Novel Therapeutic Targets in Non-Hodgkin Lymphoma [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 4501.
Abstract 1688: CRISPR-Drug combinatorial screening identifies effective combination treatments for <i>MTAP</i> null cancer
Authors: Nikola Knoll, Sarah Masser, Devishi Kesar, Eliana Destefanis, Guangyan Li, Blanka Bordas, Jayu Jen, Yao He, Srivatsan Raghavan, William Sellers, Kathleen M. Mulvaney
Journal: Cancer Research (2025)

Abstract Homozygous deletion of CDKN2A/MTAP occurs frequently in non-small cell lung cancer and other solid tumors including glioblastoma and pancreatic ductal adenocarcinoma. Lung cancer remains the leading cause of cancer-related mortalities and fewer than 15% of glioblastoma or pancreatic cancer patients survive 5 years underscoring the need for more effective therapies. PRMT5 is a synthetic-lethal dependency in MTAP null tumors and an attractive therapeutic target for CDKN2A/MTAP deleted cancers. A new revolutionary class of inhibitors, referred to as MTA-cooperative PRMT5 inhibitors, has shown promising results in ongoing early phase clinical trials. Nonetheless, effective cancer treatment typically requires therapeutic combinations to improve response rates and defeat emergent resistant clones. Thus, we sought to determine whether perturbation of other pathways could improve the efficacy of MTA-cooperative PRMT5 inhibitors. Using a paralog and single gene targeting CRISPR library we screened MTAP deleted cancers in the presence or absence of PRMT5 inhibitors. We identified several genes sensitizing to PRMT5 inhibition including members of the MAP kinase pathway. We demonstrate that genetic depletion or chemical inhibition of MAP kinase pathway members using KRAS, MEK, ERK, and RAF inhibitors synergize with PRMT5 inhibition to kill CDKN2A/MTAP null, RAS-active tumors. Further, MTA-cooperative PRMT5 inhibitors combined with either KRAS or RAF inhibitors led to durable in vivo complete responses, emphasizing the potential benefit for patients. Citation Format: Nikola Knoll, Sarah Masser, Devishi Kesar, Eliana Destefanis, Guangyan Li, Blanka Bordas, Jayu Jen, Yao He, Srivatsan Raghavan, William Sellers, Kathleen M. Mulvaney. CRISPR-Drug combinatorial screening identifies effective combination treatments for MTAP null 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 1688.
Abstract 6598: MET gene polymorphisms and breast cancer: A study of Nigerian patients
Authors: Emeka Eze Joshua Iweala, Doris N. Amuji
Journal: Cancer Research (2025)

Abstract Breast cancer (BC) remains a major cause of cancer-related mortality among women worldwide. Genetic polymorphisms, such as those in the Mesenchymal Epithelial Transition (MET) proto-oncogene, may influence susceptibility and tumor progression as seen in gastric, liver, and thyroid cancer in Japanese and Chinese populations. This study evaluated the association between three MET gene single nucleotide polymorphisms (SNPs) namely rs40239, rs1621, and rs41736 and breast cancer risk and tumor grade among Nigerian women. A case-control study was conducted with 150 participants, comprising 75 breast cancer patients and 75 healthy controls. DNA was extracted from blood samples and genotyped using the TaqMan SNP assay. Genotype and allele frequencies for the SNPs were compared between the groups, and associations with BC risk were evaluated using the chi-square test and odds ratios (ORs). In addition, ordinal regression analysis was performed to assess the relationship between SNP (rs1621) and tumor grade. Genotyping revealed distinct distributions of genotype in both groups. For rs40239, the AA genotype was more frequent in controls (60%) than in cases (17%), though the association with BC risk was not statistically significant (OR=4.706, 95% CI: 0.959-23.096, p=0.062). No significant associations were observed for rs1621 (OR=1.188, 95% CI: 0.516-2.733, p=0.426) or rs41736 (OR=0.954, 95% CI: 0.904-1.006, p=0.262). The mutant allele rs1621 was associated with reduced odds of being in a higher tumor grade (OR=0.475), suggesting a potential protective effect against aggressive tumors. However, this association was not statistically significant (p=0.090, 95% CI: -1.606-0.116). While rs1621 showed a non-significant trend towards a protective role against higher tumor grades, no statistically significant associations were observed between the examined SNPs (rs40239, rs1621, and rs41736) and breast cancer risk. Future research should focus on expanding sample sizes, including diverse African populations, and exploring the role of genetic variants in breast cancer predisposition and progression. Citation Format: Emeka Eze Joshua Iweala, Doris N. Amuji. MET gene polymorphisms and breast cancer: A study of Nigerian patients [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 6598.
Abstract 1697: Chemotherapy combined with fatty acid oxidation inhibition completely regressed tumor growth in a pancreatic cancer model
Authors: Sang Myung Woo, Chae Young Kim, Woojin Ham, Joon Hee Kang, Mingyu Kang, Woosol Hong, Jeong Hwan Park, Wonyoung Choi, Soo Youl Kim
Journal: Cancer Research (2025)

Abstract Purpose: We found that most ATP production in cancer cells depends on fatty acid oxidation (FAO). Most chemotherapeutic reagents including FOLFIRINOX regimen targeted anabolic metabolism of cancer cells such as DNA replication. All synthesis mechanisms require ATP for chemical reactions. Therefore, we proposed that blocking FAO together with chemotherapeutics may synergize anti-cancer effect by suppressing cancer growth metabolism. Experimental Design: To block FAO, CAC (carnitine-acylcarnitine carrier, gene: SLC25A20) in the mitochondria inner membrane and ACAA1 (acetyl-CoA acyltransferase1, gene: ACAA1) in the peroxisome were targeted for inhibition. KN510 was selected for CAC inhibition, and KN713 was selected for ACAA1 inhibition. To achieve maximum anti-cancer effect of FAO inhibition, KN510 and KN713 were combined for the treatment as KN510713. Anti-cancer effect was examined by xenograft model using human pancreatic cancer cells. Synergy of KN510713 with chemotherapeutic drugs also tested using a xenograft model. Results: Chemotherapy combined with KN510713 showed synergistic anti-cancer effect on 11 cancer types in in vitro analysis. Furthermore, xenograft pancreatic cancer showed completely suppressed effect of KN510713 treated with chemotherapeutics such as irinotecan only or FOLFIRINOX regimen. Conclusion: FAO inhibition stopped tumor growth by ATP depletion in pancreatic cancer. The changes in molecular signaling upon FAO inhibition revealed that ATP levels are a key regulator of all signaling. This suggests that whatever the signaling induced by the growth receptor, ATP down-regulation through FAO inhibition may provide a novel therapeutic effect. Thus, combinations of chemotherapeutic agents with FAO inhibitors have shown excellent anti-cancer activity in mice. Citation Format: Sang Myung Woo, Chae Young Kim, Woojin Ham, Joon Hee Kang, Mingyu Kang, Woosol Hong, Jeong Hwan Park, Wonyoung Choi, Soo Youl Kim. Chemotherapy combined with fatty acid oxidation inhibition completely regressed tumor growth in a pancreatic cancer model [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 1697.
Abstract 2691: Configurable multiplex immunofluorescence panels for emerging ADC targets
Authors: Yvette Cajigas, Cassandra Kysilovsky, Lauren Duro, Kevin Hwang, Lorenz Rognoni, Angela Vasaturo
Journal: Cancer Research (2025)

Abstract Background: Antibody-drug conjugates (ADCs) are revolutionizing oncology by selectively delivering cytotoxic payloads to cancer cells while sparing healthy tissues. ADC targets are typically cell-surface proteins overexpressed on tumor cells but with limited expression on normal cells, making spatial proteomics assays an ideal complement to this research. However, standard DAB-based immunohistochemistry techniques often lack the specificity and sensitivity needed to confidently quantify the target expression level in tumors with low target abundance, which can result in discordant scoring by pathologists. To support ADC drug development, we present a flexible and scalable approach to the design, development, and validation of mIF panels tailored to ADC targets using the highly sensitive InSituPlex (ISP) technology. Methods: Antibodies targeting ADC-specific markers were initially optimized using DAB chromogenic staining. Following this, antibodies were conjugated to DNA barcodes, and titrations of both antibodies and fluorophores were performed to achieve optimal signal intensity and staining patterns as evaluated by a pathologist. Singleplex DAB and ISP assays were conducted on serial FFPE sections across multiple tumor types. Validation experiments were designed and performed to test the platform's precision and configurability for ADC-related targets. AI-driven STARVUE software was used for image analysis and assessment of reproducibility of key metrics including cell density and signal intensity. Results: This approach integrates adaptability to diverse ADC targets, optimized antibody titration, fluorophore selection, and panel construction, achieving high specificity and sensitivity for multiple biomarkers in a single tissue section. The inclusion of STARVUE image analysis enhances the evaluation of spatial relationships between ADC targets and downstream effectors, offering a deeper understanding of drug efficacy and resistance mechanisms. The platform demonstrated high concordance across configurations, with single-target coefficients of variation (CVs) consistently below 20%. Spatial and intensity metrics further confirmed the robustness of the assay in multiple tumor types. Conclusions: This validated and scalable mIF platform for ADC targets represents a significant advancement in spatial proteomics, providing a robust solution for researchers and clinicians to accelerate ADC development, optimize therapeutic strategies, and improve clinical outcomes. Citation Format: Yvette Cajigas, Cassandra Kysilovsky, Lauren Duro, Kevin Hwang, Lorenz Rognoni, Angela Vasaturo. Configurable multiplex immunofluorescence panels for emerging ADC targets [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 2691.