tbuckley/cabot-search huggingface dataset:
Abstract 5229: From the patient to the culture plate and beyond: Challenges and opportunities in cancer-associated fibroblast research
Authors: Felix De Vuyst, Sam Ernst, Stephanie Vermeulen, Zihan Xia, Sándor Dedeyne, Olivier De Wever
Journal: Cancer Research (2025)

Abstract Cancer-associated fibroblasts (CAFs) are a key component of the microenvironment of various solid tumor types. Due to their critical role in tumor progression and therapy resistance, a surge in CAF-related publications is observed exploring the functionality, heterogeneity and potential as therapeutic targets. To facilitate community wide data consolidation and sharing, we initiated a crowdsourcing data-repository together with both national and international collaborators. With this initiative we mapped 85 general and CAF-specific experimental, biological and functional parameters from more than 1000 CAF-related publications from the past decade. This unique set of data indicates a general heterogeneity and underreporting of crucial experimental parameters, related to isolation procedures, culture conditions and CAF characterization. Using single-cell RNAseq we were able to show a phenotypic shift in the CAF population going from the in vivo situation to an in vitro culture. Additionally, we empirically investigated the impact of in vitro aging and hTERT immortalization on the stability of this obtained in vitro CAF phenotype. At the molecular level, single cell RNAseq, bulk proteomics, flow cytometry and Luminex cytokine assay revealed a specific gene/protein and pathway rewiring upon passaging of primary CAF cultures, while immortalization resulted in a loss of heterogeneity in the culture but with gain of phenotype stability. Functional assays evaluating collective migration and type I collagen invasion confirmed the increased phenotypic stability in hTERT immortalized CAF cultures. In conclusion, CAF literature mining combined with empirical evaluation will further support interpretable, reproducible and transparent experimental reporting in the CAF research field. Citation Format: Felix De Vuyst, Sam Ernst, Stephanie Vermeulen, Zihan Xia, Sándor Dedeyne, Olivier De Wever. From the patient to the culture plate and beyond: Challenges and opportunities in cancer-associated fibroblast research [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 5229.
Abstract 5201: Modeling human mammary epithelial lineages using patient-derived organoid cultures
Authors: David A. Rowbotham, Samantha Rothwell, Sharon A. Louis, Allen C. Eaves, John Stingl
Journal: Cancer Research (2025)

Abstract Organoids have emerged as a powerful model for studying normal and tumor cell biology; however, the application of organoid technology for culturing human breast epithelial cells has been challenging due to the difficulty in maintaining estrogen receptor (ER)-expressing cells in culture. To address this problem, we have developed MammoCult™ Organoid Kit (Human), a modular serum- and phenol red-free cell culture kit that promotes the growth of multilineage organoids, as well as organoids composed solely of ER+ and ER- luminal or basal cells. Primary human breast cells from reduction mammoplasty tissues from both pre- and postmenopausal donors were dissociated and seeded in 3D extracellular matrix domes, as either single cells or tissue fragments. Organoids were typically dissociated and passaged every 10 - 20 days. Cultures were analyzed by flow cytometry and immunocytochemistry for the expression of the pan epithelial marker EpCAM, the luminal markers Keratin 8 (K8), KIT, ER, MUC1, progesterone receptor (PR), and the basal markers CD49f, smooth muscle actin (SMA), and K14. Organoid cultures initiated from single cell suspensions generated distinct organoid morphologies reflective of their cell of origin. Luminal cells generated small hollow cystic organoids composed predominantly of cells that expressed K8, MUC1, and variable levels of expression of ER, PR, and KIT (n = 6 - 12). Notably, ER expression was maintained in luminal organoids for a minimum of 5 passages when split at a 1:3 to 1:5 split ratio (n = 3). Basal cells seeded in Corning® Matrigel® supplemented with collagen I (2 mg/mL) formed terminal ductal lobular unit (TDLU)-like branching structures that were composed solely of K14+SMA+ basal cells and could be passaged for a minimum of 2 passages when co-seeded with human mammary fibroblasts (n = 3). Multilineage organoids composed of both luminal and basal cells could be generated when cell aggregates or tissue fragments were initially seeded (n = 5). These results demonstrate that the MammoCult™ Organoid Kit (Human) offers a robust, in vitro model system for studying human mammary gland biology. Citation Format: David A. Rowbotham, Samantha Rothwell, Sharon A. Louis, Allen C. Eaves, John Stingl. Modeling human mammary epithelial lineages using patient-derived organoid cultures [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 5201.
Abstract 2391: Comprehensive quantification and annotation of viral gene integration and expression across thousands of human cancer models
Authors: Sowmya Iyer, Moore van Tienen, Phillipp Trollman, Yao He, William R. Sellers, Catarina D. Campbell
Journal: Cancer Research (2025)

Viral infections have been demonstrated to influence host gene expression and drive tumorigenesis. This study aims to systematically annotate genome integration and expression of ∼3000 exogenous and human-endogenous viral species across all public DepMap cancer cell lines, representing a diverse set of cancer types and lineages. Our preliminary results from this analysis pipeline successfully recapitulated known Human Papillomavirus (HpV strains 16, 18, 30 and 53) signatures in 12 cervical, 2 head and neck, and 4 engineered prostate cancer cell lines, demonstrating sensitivity at both the strain and gene levels. Associating these with genome-wide CRISPR screening data, we identified dependencies that were more correlated with viral presence rather than their respective lineages. Additionally, we observed expression of Epstein-Barr Virus(EBV) in multiple cancer types, a majority of which were of lymphoid lineage. We also found expression of the env gene of Human Endogenous Retrovirus-K (HERV-K113) in multiple lineages, with the highest average expression in skin cancers. By analyzing whole-genome sequencing we seek to identify viral integration sites in the cell lines’ genomes, to complement viral gene expression. From this large-scale multimodal analysis of features derived from genomic and transcriptomic data combined with gene dependencies, we aim to uncover potential viral contributions to oncogenesis and biomarker or target discovery. This will provide a foundational resource for understanding the role of viruses in cancer, offering new insights into viral-driven mechanisms of disease. Citation Format: Sowmya Iyer, Moore van Tienen, Phillipp Trollman, Yao He, William R. Sellers, Catarina D. Campbell. Comprehensive quantification and annotation of viral gene integration and expression across thousands of human cancer 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 2391.
Abstract 3056: Structural optimization of lapatinib analogs for overcoming CNS metastases in breast cancer
Authors: Mostafa Mohammed Ahmed Aref, Eneye D. Ajayi, Md A. Emran Hossain, Rokaia S. Abdullah, Hamed I. Ali
Journal: Cancer Research (2025)

Abstract Due to its role in aggressive disease progression and poor clinical outcomes, HER-2 kinase was considered a vital target in breast cancer (BC). Central nervous system (CNS) metastases represent a significant challenge in HER2+ BC, as they are often refractory to existing therapies such as lapatinib. Our previous work focused on the structural optimization of lapatinib analogs to enhance potency, selectivity, and pharmacokinetics. The HER2-selective derivatives were synthesized and characterized, with nanomolar IC50 values range of [5.4-12 nM], more the reference drug lapatinib (IC50: 95.5 nM). Compound 17d demonstrated outstanding HER2 selectivity and minimal off-target kinase activation. Broad-spectrum activity was observed (GI50: 1.43-2.09 µM), with a strong preference for HER2+ BC cells over HER2− cells, achieving up to 20-fold selectivity in antiproliferative assays. Compound 17d emerges as a promising candidate with the potential to overcome the limitations of current HER2 therapies. Its potent HER2-selective inhibition, robust in vivo efficacy, and favorable pharmacokinetic profile highlight its therapeutic potential for HER2+ breast cancer. Our current study mainly focuses on the structural optimization of our lead compound to be more BBB penetrable to overcome the HER-2 CNS Metastatic cancers by applying in-silico, in-vitro, and in-vivo models. Citation Format: Mostafa Mohammed Ahmed Aref, Eneye D. Ajayi, Md A. Emran Hossain, Rokaia S. Abdullah, Hamed I. Ali. Structural optimization of lapatinib analogs for overcoming CNS metastases in 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 3056.
Abstract 5639: A potent aminosteroid (RM-581) that inhibits orally in mice the tumor growth in an orthotopic xenograft pancreatic cancer model
Authors: Donald Poirier, Qi Chen, René Maltais, Jenny Roy, Forkan Ahamed, Shannon Arnold
Journal: Cancer Research (2025)

Abstract Pancreatic cancer has a very poor prognosis, with a 5-year survival rate of only 10%, making it imperative to develop effective small molecules as new drugs. The aim of this study was to validate the in vitro and in vivo efficacy of a promising endoplasmic reticulum-stress aggravator, the synthetic aminosteroid RM-581, that induces apoptosis, as a potential treatment for pancreatic cancer. When tested on a panel of human (PANC-1, MIACaPa2, L3.6, CAPAN-1, BxPC3) and murine (Pan02) pancreatic cancer cells, RM-581 strongly reduced their proliferation (IC50 = 0.83, 0.45, 2.10, 0.78, 5.75 and 1.77 μM, respectively), which justified its evaluation in a PANC-1-Luc cell-derived orthotopic xenograft model in nu/nu mice. After 5 weeks of oral treatment with RM-581 by gavage (po) daily, in vivo fluorescence imaging (IVIS) imaging showed inhibited tumor growth of 11, 54 and 76% at 10, 40 and 80 mg/kg, respectively, compared to the untreated control group. Compared with a cholesterol biosynthesis inhibitor pravastatin (4 mg/kg/subcutaneous (sc)), the effect of RM-581 was similar at 40 mg/kg/po and greater at 80 mg/kg/po. Inhibitions obtained with RM-581 and pravastatin were also confirmed by tumor weight measurement at necropsy. A comparison with antineoplastic drug docetaxel (4 mg/kg/intraperitoneal/2 x weekly) was however not possible, since several toxicities were found after 2 weeks of treatment, forcing euthanasia of the mice. From histological evaluation (hematoxylin and eosin staining), no differences were found in the liver, kidney and spleen in all groups, which is consistent with the clinical observation of no signs of toxicities and no differences in body weight for RM-581 treatments. In summary, RM-581 is therefore a promising candidate for a possible oral treatment of pancreatic cancer. Citation Format: Donald Poirier, Qi Chen, René Maltais, Jenny Roy, Forkan Ahamed, Shannon Arnold. A potent aminosteroid (RM-581) that inhibits orally in mice the tumor growth in an orthotopic xenograft 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 5639.
Abstract 5223: Deciphering cellular heterogeneity and therapeutic responses in NSCLC through scRNA-seq analysis
Authors: Hwajin Choi, Kyoung-Ho Pyo, Sun Min Lim, Byoung Chul Cho, Seunghee Hong
Journal: Cancer Research (2025)

Abstract Programmed cell death protein and its ligand (PD-1 / PD-L1) blockades have been approved for the treatment of metastatic non-small cell lung cancer (NSCLC). PD-L1 binds to PD-1 and functions as a co-inhibitory factor. It is well known that in cancer, PD-L1 is highly expressed hence cancer cells can evade the host immunity in the tumor microenvironment (TME). Although PD-1 / PD-L1 blockades have been clinically utilized, the biological factors determining treatment outcome remain convoluted. An in-depth investigation of cellular heterogeneity including both cell subtypes and states (defined by cellular biomolecular programming) will provide foundational evidence for clinicians and researchers to improve PD-1 / PD-L1 immunotherapeutic practice. The recent decade has shown an explosive growth of single-cell RNA sequencing (scRNA-seq) to study biomedical phenomena. In contrast to bulk RNA-seq, scRNA-seq enables researchers to properly decipher and analyze the complex cellular heterogeneity. Our scRNA-seq data spans 674, 609 cells populating early, late, metastatic stage lung cancer and the normal lung tissues from 100 subjects. Especially, part of our metastatic samples harbor classification based on the existence of immune checkpoint blockade (ICB) treatment and therapeutic efficacy of the treatment. Our scRNA-seq analysis results thoroughly provide an intensive comprehension of dysregulation in T cells. This single-cell analysis potentially reveals pathways targeted by immunotherapy and discovers possible therapeutic targets which could be combined with the current immunotherapy for the synergistic effects. Citation Format: Hwajin Choi, Kyoung-Ho Pyo, Sun Min Lim, Byoung Chul Cho, Seunghee Hong. Deciphering cellular heterogeneity and therapeutic responses in NSCLC through scRNA-seq analysis [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 5223.
Abstract 2378: Developing new potent therapeutic strategies for neuroendocrine carcinomas
Authors: Tanya Ivanova Stoyanova
Journal: Cancer Research (2025)

Abstract Neuroendocrine carcinomas, such as neuroendocrine prostate cancer (NEPC), small cell lung cancer (SCLC), and neuroblastoma, share common histological features, including expression of neuroendocrine markers, rapid relapse after treatment, and poor prognosis. Due to the poor clinical outcome of patients with neuroendocrine carcinomas, there is a critical need to identify new drivers, therapeutic targets, and effective therapeutic strategies for these malignancies. Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a protease that has a dual function in regulating protein stability. We demonstrated that UCHL1 is significantly elevated in tissues from patients with NEPC, SCLC, and neuroblastoma. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 stabilizes POM121 to regulate POM121-associated nuclear transport of key transcriptional factors, E2F1 and c-MYC. Here, we developed novel and more potent UCHL1 small molecule inhibitors as a new therapeutic strategy to target neuroendocrine carcinomas. Our new compounds demonstrate high potency with safety profile in vivo for neuroendocrine carcinomas. Importantly, treatment with UCHL1 inhibitors significantly reduces tumor growth of neuroendocrine carcinomas in pre-clinical settings. Our study reveals new mechanisms of UCHL1 function in neuroendocrine carcinomas tumorigenesis, identifies UCHL1 as a therapeutic target and potential molecular indicator for diagnosis and monitoring treatment responses in neuroendocrine carcinomas and develops new inhibitors to target UCHL1. Citation Format: Tanya Ivanova Stoyanova. Developing new potent therapeutic strategies for neuroendocrine carcinomas [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 2378.
Abstract 5227: Extrachromosomal MYC-paralogs amplification shapes suppressive tumor microenvironment in small cell lung cancer
Authors: Jingwei Zhang, Yueqi Jin, Ence Yang, Xiao Li
Journal: Cancer Research (2025)

Abstract Introduction: Although immunotherapy has demonstrated promise in small cell lung cancer (SCLC), certain patients encounter limited benefits, highlighting the need for identifying immunosuppressive biomarkers. Extrachromosomal circular DNA (ecDNA) promotes amplification of MYC-paralogs, which drive cross-resistance in SCLC. Here, we aim to investigate whether ecDNA-mediated MYC-paralogs amplification (ecMYC+) represents immunosuppressive features in SCLC. Methods: Bulk RNA sequencing (RNA-seq) data were retrieved from public database and paraffin-embedded samples (n = 40). The copy number of MYC-paralogs was investigated using real-time polymerase chain reaction. RNA-seq, flow cytometry and metaphase fluorescence in situ hybridization (FISH) were performed in SCLC cell lines. The overexpression and amplification of MYC-paralogs in SCLC clinical samples (n = 42) were identified using immunohistochemistry (IHC) and FISH. The spatial distribution of tumor immune microenvironment (TIME) was characterized by multiplex immunofluorescence and imaging mass cytometry (IMC). Results: The mean copy number of ecDNAs was higher in SCLC than in the other cell lines (15.3 vs 8.4, p = 4.0×10-3), and the frequency of ecMYC+ cell lines was higher in SCLC than that in the other lineages (SCLC 22/47 vs others 15/282, p = 3.9×10 -12). In ecMYC+ SCLC, multiple immune-related pathways were down-regulated, while nucleotide metabolism processes were up-regulated. Inhibition of nucleotide metabolism by hydroxyurea and gemcitabine resulted in the reduction of ecDNA, along with the activation of antigen presenting pathways. Immunohistochemical analysis revealed that overexpression of MYC-paralogs was observed in 19 out of 42 resected SCLC samples. FISH identified 8 samples as MYC-paralogs copy number gain or amplification, and 3 samples exhibited a scattered signals distribution resembling ecDNA amplification. Through the resolution of 103, 341 cells from 24 pathological regions, we observed higher expression of MKI67, VEGFA, FAP and FOXP3 and reduced T cell infiltration in ecMYC+ samples. Moreover, ecMYC+ samples exhibited elevated cellular neighborhoods dominated by Ki67+ tumors, with reduced spatial interaction with immune cells. Conclusions: Extrachromosomal amplification of MYC-paralogs shapes suppressive tumor microenvironment, identifying potential subgroup of immunotherapy resistant patients. Citation Format: Jingwei Zhang, Yueqi Jin, Ence Yang, Xiao Li. Extrachromosomal MYC-paralogs amplification shapes suppressive tumor microenvironment 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 5227.
Abstract 2365: Determining the role of pregnancy-induced IgG antibodies in parity-associated mammary oncoprotection
Authors: Dhivyaa Anandan, Marygrace Trousdell, Amritha Varshini Hanasoge Somasundara, Johannes T.-H. Yeh, Camila O. dos Santos
Journal: Cancer Research (2025)

Abstract An early age of first pregnancy reduces the lifelong risk of developing breast cancer (BC) by ∼30%. The dos Santos Lab has shown that pregnancy-induced alterations to the mammary immune microenvironment, including adaptive immune cells, are crucial for the oncoprotective effect of pregnancy. While plasma cells and memory B cells in the pregnant/lactating mammary gland (MG) are largely appreciated for their role in secreting antibodies into breastmilk, B cells may also encounter and secrete antibodies against self-antigens that arise during pregnancy-associated MG development and milk synthesis. Several antigens expressed in the pregnant/lactating MG are also expressed in BC. As a result, we hypothesize that pregnancy induces IgG production against antigens associated with pregnancy and mammary tumorigenesis, contributing to parity-associated mammary oncoprotection. To obtain an unbiased profile of pregnancy-induced alterations to the mammary immune microenvironment, we performed single cell RNA-sequencing on virgin and parous non-tumor-bearing mammary tissue from a mouse model of pregnancy-induced mammary oncoprotection (Brca1 loss of function). Our analysis reveals an enrichment of plasma cells and memory B cells in the parous MG, raising the question of whether these cells and their antibody production may play a role in the inhibition of mammary tumorigenesis in parous mice in this model. To understand whether pregnancy induces alterations to the antigens recognized by B cells, we performed BCR-sequencing of MGs from virgin and parous wildtype mice. Using clonotype abundance analysis, we identified five IgG clonotypes that were most abundant and unique to the parous MGs. We used the BCR sequences of these clonotypes to synthesize five recombinant pregnancy-induced IgG antibodies. Through immunofluorescent staining analysis of mammary tissue from various stages of development and tumorigenesis, we have identified three clones that bind to pregnancy-induced mammary epithelial antigens that are also present in virgin pre-neoplastic mammary tissue. These results suggest that pregnancy may influence the BCR repertoire and enable IgG production against antigens expressed by pre-neoplastic cells in the MG. We are testing whether these recombinant pregnancy-induced IgG antibodies can be administered in vivo and inhibit mammary tumorigenesis in mouse models of BC. Citation Format: Dhivyaa Anandan, Marygrace Trousdell, Amritha Varshini Hanasoge Somasundara, Johannes T.-H. Yeh, Camila O. dos Santos. Determining the role of pregnancy-induced IgG antibodies in parity-associated mammary oncoprotection [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 2365.