tbuckley/cabot-search huggingface dataset:
Abstract 1105: Development of an in-house methodology to analyze large clinical cancer biomarkers datasets
Authors: Tariq Arshad, Nikhil Wilkins, Gilles Tapolsky, Mike Gazda
Journal: Cancer Research (2025)

Abstract Background: BXQ-350 is a novel biologic that modulates sphingolipid metabolism. BXQ-350 is currently being investigated in several clinical studies. Multiple biomarker samples are collected in the course of these studies to support clinical development and illustrate the mechanism of action, support patient selection, and associate response with trends. The resulting large data set associated with these different biomarkers requires an analytical tool to process the data. To meet those ends, Bexion Pharmaceuticals developed an in-house analytical method to perform analysis on these data points. The platform performs data wrangling, processing, calculations, and produces statistical and graphical outputs from multiple different input sources. Methods: The analytical methodology was developed using Python v3.13 and open-source modules. Windows Excel files are used for the input and are formatted in Excel to be properly read. The outputs are statistical Excel files and graphical visualization of the data. Analytical Methodology 1. Import Excel file and create a pandas dataframe object 2. Merge dataframes based on patient identification 3. Perform data wrangling on the merged dataframe Create or update a MySQL table if applicable 4. Process the data and perform calculations, including QC samples incorporated in each analysis 5. Perform statistical analysis of QC samples to determine which changes would be statistically significant 6. Perform a second round of processing and calculations on data that passed QC 7. Group and separate data for output handling 8. Create graphs and tables Results: The analytical methodology was designed to analyze any type of biomarker data set, allowing the comparison of results across biomarkers and supporting analysis of potential correlations. Serial analysis can compare trends in biomarkers results and clinical outcome(s). In addition, statistics are derived for both individual patients and groups to stratify the data. Conclusion: Large biomarker data sets are collected in the course of clinical studies to support clinical development. Furthermore, such analyses can support understanding the mechanism of action and guide patient selection. The method developed allows for flexible and granular analysis of biomarkers and correlative analysis across different groups of biomarkers or individual patients and groups of patients Citation Format: Tariq Arshad, Nikhil Wilkins, Gilles Tapolsky, Mike Gazda. Development of an in-house methodology to analyze large clinical cancer biomarkers datasets [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 1105.
Abstract 326: Chemotherapies change the NRF2 levels and impact the differentiation and growth of human high grade serous ovarian cancer
Authors: Chelsea Katz, Helen Toma, Yaas Azmoudeh, Nasrine Bendjilali, Huseyin Karaduman, Hadi Shojaei, Gord Zhu, Lauren Krill, Chu Christina, Yemin Wang
Journal: Cancer Research (2025)

Abstract NRF2, an antioxidant gene and anti-inflammatory pathway, is altered in about 50% of high grade serous ovarian cancer (HGSOC), the most aggressive type of ovarian cancer. NRF2 is implicated in the resistance to chemotherapies in several types of cancers. We aimed to understand if treatment with carboplatin or paclitaxel impacts the levels of NRF2 and if that changes the differentiation, growth, and metastasis of HGSOC. We used OVCAR8, a human HGSOC cell line with a basal level of NRF2, and induced overexpression of NRF2 using pIND20 system with NRF2E79Q mutation (one of the most common mutations of NRF2 found in human tumors). Our results showed high growth and invasion in high-NRF2 tumor cells compared to low-NRF2 tumor cells with and without chemotherapies. Treatment with carboplatin inhibits the levels of NRF2 in low-and high-NRF2 versions of OVCAR8. Carboplatin also inhibits the MYC, P63, and CD274 (PD-L1) protein levels, and the epithelial to mesenchymal transition (EMT) pathway (Vimentin). Additionally, in high-NRF2 tumor cells, paclitaxel increases the levels of NRF2, MYC, CD274 (PD-L1), and Vimentin, and decreases the levels of P63. In contrast, low-NRF2 tumor cells treated with paclitaxel show decreased MYC, CD274 (PD-L1) and Vimentin and increased P63. These changes impact the growth and metastasis (by scratch test) of OVCAR8. We found that carboplatin inhibits the growth and invasion while paclitaxel increases the growth and invasion in the high-NRF2 version of OVCAR8. These studies show that carboplatin might be a good option as a single treatment compared to paclitaxel. In addition to the increase in NRF2 and differentiation markers that support the tumor cell growth, paclitaxel also increased the PD-L1 protein levels in high-NRF2 tumor cells which might enhance the efficacy of anti-PDL1. Therefore, combination immunotherapy (anti-PDL1) with paclitaxel may have therapeutic benefit in patients with high-NRF2 HGSOC. Citation Format: Chelsea Katz, Helen Toma, Yaas Azmoudeh, Nasrine Bendjilali, Huseyin Karaduman, Hadi Shojaei, Gord Zhu, Lauren Krill, Chu Christina, Yemin Wang. Chemotherapies change the NRF2 levels and impact the differentiation and growth of human high grade serous ovarian 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 326.
Abstract 204: Targeting tumor-stroma interactions: Prognostic and therapeutic implications of the ACVR1-BMP7 axis in colorectal cancer
Authors: Norikatsu Miyoshi, Shinya Kato, Shiki Fujino, Soichiro Minami, Rie Mizumoto, Rie Hayashi, Kengo Haruma
Journal: Cancer Research (2025)

Abstract The tumor microenvironment plays a critical role in colorectal cancer (CRC) progression, with stromal signatures closely linked to poor prognoses and resistance to chemotherapy. These stromal factors significantly influence tumor dynamics, promoting progression, relapse, and overall worse outcomes. Among these, cancer-associated fibroblasts (CAFs) have gained attention due to their heterogeneity and functional contributions to the tumor microenvironment. Although single-cell analysis has identified distinct CAF subpopulations, molecular-targeted therapies against CAFs remain lacking, highlighting a critical clinical need. To address this, the study utilized organoid culture methods replicating CRC histological architecture. Two-dimensional organoids (2DO) provided a novel platform to study tumor-stromal interactions, facilitating the investigation of cancer-fibroblast crosstalk. The focus was on signaling pathways, specifically the interplay between Activin receptor type I (ACVR1) in fibroblasts and Bone morphogenetic protein 7 (BMP7) in cancer cells, as potential therapeutic targets. Using single-cell analysis and patient-derived models, the study examined the prognostic significance of ACVR1 and BMP7 expression in CRC, especially in stage II patients. Single-cell RNA sequencing identified fibroblast subpopulations, revealing a previously unexplored BMP7-ACVR1 signaling axis. High BMP7 and ACVR1 expression levels were significantly associated with poorer disease-free survival (DFS) and overall survival (OS), emphasizing their prognostic value. Clinical data from stage II patients supported this finding, linking elevated BMP7 and ACVR1 levels to adverse outcomes. The functional role of the BMP7-ACVR1 axis was validated with a 2DO-based mouse xenograft model, which reflected the stromal heterogeneity of human CRC tumors. Tumor growth was significantly inhibited by administering an ACVR1 inhibitor during 2DO-mouse stromal cell co-culture, highlighting the therapeutic potential of targeting ACVR1. This underscores the critical role of CAFs in tumor progression and their potential as therapeutic targets. In conclusion, the study identifies ACVR1 as a promising therapeutic target regulating CAF proliferation, influencing tumor growth and patient outcomes. The prognostic significance of BMP7 and ACVR1 further underscores their potential as biomarkers in stage II CRC. Citation Format: Norikatsu Miyoshi, Shinya Kato, Shiki Fujino, Soichiro Minami, Rie Mizumoto, Rie Hayashi, Kengo Haruma. Targeting tumor-stroma interactions: Prognostic and therapeutic implications of the ACVR1-BMP7 axis in colorectal 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 204.
Abstract 1068: Navigating next-generation pre-clinical models of drug discovery &amp; development with RNA-seq
Authors: Ajeet P. Singh, Rula R. Khairi, Amy L. Reese, Jade Kirkland, James Duncan, Noah Wax, Robert Marlow, Steve King, Ana Fernandes, Jonathan L. Jacobs
Journal: Cancer Research (2025)

Cell models paired with curated gene expression data are vital for preclinical research. Transcriptomic data from traceable, authenticated cell lines streamline hypothesis development and experimental design while illuminating underlying biological mechanisms. In cancer research, these models have notably identified therapeutic targets and biomarkers. To advance cancer research, ATCC® sequenced the transcriptomes of 141 immune cancer cell lines, accessible through ATCC Cell Line Land, encompassing various hematopoietic lineages. This effort provided insights into gene expression patterns, revealing potential biomarkers and gene regulatory networks tailored to specific cell lines. Utilizing this data, we conducted a comparative analysis, pinpointing genes and pathways governing cellular traits. This informed our evaluation of therapeutic molecules like the Curcumin analog EF-24. Our analysis of EF-24's effects on leukemia cell lines K562 (ATCC® CCL-243™, HL-60 (ATCC® CCL-240™), THP-1 (ATCC® TIB-202™), Kasumi-1 (ATCC® CRL-2724™) demonstrated increased cell death post-treatment. EF-24 activated pathways associated with cell survival and death regulation, notably impacting STAT1-induced cell death, and enhancing innate immune system genes. This research offers a detailed understanding of EF-24's molecular actions in tumors, emphasizing the significance of STAT1 signaling in its antitumorigenic effects. The profound impact of EF-24 on inducing cell death across multiple leukemia cell lines underscores its potential as a therapeutic agent. By elucidating its specific molecular actions and highlighting the pivotal role of STAT1 signaling, this study not only deepens our comprehension of EF-24's mechanisms but also underscores its promising value in targeted antitumorigenic strategies. Citation Format: Ajeet P. Singh, Rula R. Khairi, Amy L. Reese, Jade Kirkland, James Duncan, Noah Wax, Robert Marlow, Steve King, Ana Fernandes, Jonathan L. Jacobs. Navigating next-generation pre-clinical models of drug discovery &amp; development with RNA-seq [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 1068.
Abstract 33: Development of a humanized mouse model for γδT cells
Authors: Lydia Blot, Lopes Joaquim, Emerson Serres, Vanessa Croize, Hervé Barret, Pauline Rettman, Clément Barjon, Dorothee Bourges, Antoine Lhermitte, Valéria Fantin, Sukhvinder Sidhu, Loreley Calvet
Journal: Cancer Research (2025)

Unconventional T cells such as gamma delta (γδ) T cells have garnered significant interest in cancer immunotherapy due to their potent anti-tumor properties including strong cytotoxic capabilities in hematological malignancies and their ability to recognize a broad range of tumor antigens independent of the classical major histocompatibility complex (MHC) molecules. Given the interest in engaging these immune cell populations in cancer therapy, we established a new in vivo humanized mouse model through the adoptive transfer of human γδT cells to support this emerging area of therapeutic interest. This model was created by transplanting γδT cells sorted from PBMC donors into Fc-resolv huIL15 NOG (functional knock-out of murine Fcγ receptors to minimize the confounding impact of mouse immune cells) mice, genetically engineered to express human IL-15. We demonstrate that various γδT cell populations, including Vδ1 and Vδ2, can be successfully maintained over a long period of time, preserving the expression of critical functional biomarkers such as NKG2D, CD69 or CD16, under various engraftment conditions. Additionally, we showed that hu γδT cells display functional engagement in vivo, achieving high efficacy with epcoritamab (CD20-CD3 Ab) against disseminated tumors in the hu γδT cell adoptive transfer mouse model. Citation Format: Lydia Blot, Lopes Joaquim, Emerson Serres, Vanessa Croize, Hervé Barret, Pauline Rettman, Clément Barjon, Dorothee Bourges, Antoine Lhermitte, Valéria Fantin, Sukhvinder Sidhu, Loreley Calvet. Development of a humanized mouse model for γδT 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 33.
Abstract 1042: MAGE-A3 and PD-L1 protein co-expression in lung cancer a look at the immune cells’ tumor microenvironment
Authors: Aimee Icaza Galarza, Rachel M. Gonzalez, YiChen Guo, Dehe Kong, Bailey Gilmore, Tianli Qu, Alex Strom, Zhaoying Guo, Qi Ren, Xiaomin Hu, Ranran Zhang, Zhaohui Wu, Jessi Chen, Xuan Liu, Wei Fu
Journal: Cancer Research (2025)

Abstract This lab’s previous studies highlight the co-expression of PD-L1 (CD274) and MAGE-A3/A4 in non-small cell lung cancer (NSCLC) and squamous cell lung cancer, with around 50% of the screened tumors exhibiting this co-expression. Additionally, this study also identified MAGE-A3/A4 as a secreted protein using CytoSections. A sandwich ELISA was developed for MAGE-A3/A4 and demonstrated that serum levels of MAGE-A3 protein were significantly elevated in lung cancer patients compared to matched controls. This statistically significant difference suggests that MAGE-A3 could serve as a valuable biomarker for lung cancer diagnosis and prognosis. Such findings may also provide insights into the tumor microenvironment and the immune evasion mechanisms facilitated by PD-L1 and MAGE-A3 co-expression, potentially guiding the development of targeted therapies or combination strategies in the treatment of lung cancer. In this study, the lung cancers were screened with CD1C, CD163, CD20, CD31, CD3E, CD4, CD68, CD8A, FOXP3 immune markers previously evaluated with PD-L1 to characterize the tumor micro-environment where PDL1 and MAGE-A3 protein are co-expressed versus when only MAGE-A3 is expressed in lung cancer. MAGE-A3 was detected on positive CD3e and suggesting a role in regulating immune response. This study offers insights into the tumor microenvironment, a new view of immune escape in lung cancer, and the potential of MAGE-A3 as a diagnostic/prognostic biomarker and therapeutic target, particularly in combination with immune checkpoint inhibitors. Citation Format: Aimee Icaza Galarza, Rachel M. Gonzalez, YiChen Guo, Dehe Kong, Bailey Gilmore, Tianli Qu, Alex Strom, Zhaoying Guo, Qi Ren, Xiaomin Hu, Ranran Zhang, Zhaohui Wu, Jessi Chen, Xuan Liu, Wei Fu. MAGE-A3 and PD-L1 protein co-expression in lung cancer a look at the immune cells’ tumor microenvironment [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 1042.
Abstract 1614: Ferroptosis mediated cell death in colorectal cancer cells through oxidative stress
Authors: Mohamed A. Eltokhy, Shreyas R. Gaikwad, Morgan Moore, Sanjay K. Srivastava
Journal: Cancer Research (2025)

Abstract Ferroptosis, a regulated form of non-apoptotic cell death, occurs due to lipid peroxide accumulation resulting from impaired cellular antioxidant defenses, particularly the inactivation of glutathione peroxidase 4 (GPX4). This process has gained attention as a novel therapeutic target, particularly for colorectal cancer (CRC), a malignancy often resistant to conventional apoptosis-based therapies. Our study investigated the anticancer potential of HLN, an antimicrobial agent. The cytotoxicity of HLN was evaluated in CT26, HCT116 &amp; HT29 cell lines by SRB assay. To confirm HLN-induced ferroptosis, we employed ferro-orange staining to detect lipid peroxidation, GSH and malondialdehyde (MDA) assays to quantify oxidative damage. Mitochondrial membrane potential and ROS generation were determined by flow cytometry, Western blotting was used to determine GPX4, GPX1, NRF2, KEAP1 and SLC7A11/xCT expression in CRC cells. HLN exhibited significant cytotoxic effects across all CRC cell lines, with IC50 values ranging from 1-4 μM. Ferro-orange staining and MDA assays confirmed extensive lipid peroxidation by HLN treatment. HLN treatment also significantly depleted intracellular GSH levels and depolarized mitochondrial membrane, whereas increased ROS production, indicating oxidative stress. Western blot results showed reduced GPX4 and SLC7A11/xCT as well as modulation in ferroptotic markers, such as GPX1, NRF2, KEAP1, by HLN treatment. In conclusion our data suggests that HLN induces ferroptosis in CRC cells by promoting lipid peroxidation, mitochondrial dysfunction, and oxidative stress Citation Format: Mohamed A. Eltokhy, Shreyas R. Gaikwad, Morgan Moore, Sanjay K. Srivastava. Ferroptosis mediated cell death in colorectal cancer cells through oxidative stress [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 1614.
Abstract 858: Development of next generation carbohydrate-based vaccines
Authors: Xuefei Huang
Journal: Cancer Research (2025)

Abstract The development of an effective vaccine construct against tumor associated carbohydrate antigens (TACAs) is an attractive approach towards cancer treatment and prevention. However, a significant challenge is that TACAs are only weakly immunogenic and direct administration of TACAs cannot elicit a powerful antibody response to protect the host from cancer development. In this presentation, we will present our strategies in engineering virus like particle bacteriophage Qβ to significantly enhance the immunogenicity of TACAs as potential anti-cancer vaccines. With its abilities to display antigens in a highly organized manner, Qβ can be a powerful carrier to deliver the antigen to the immune system and activate adaptive immunity. We have engineered Qβ to reduce the antibody responses against the carrier and incorporate T cell epitopes to induce a comprehensive immune response activating both humoral and cellular immunity. With the new Qβ carrier in hand, ganglioside GD2 has been explored as a representative antigen. Ganglioside GD2 is an appealing TACA due to its overexpression on many types of tumor cells. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qβ-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans. Building on these results, we are further engineering the 9NHAc-GD2 antigen to improve its immunogenicity. Our latest efforts in designing new GD2 antigens and evaluating them in tumor models will be discussed. Citation Format: Xuefei Huang. Development of next generation carbohydrate-based vaccines [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 858.
Abstract 761: Shared and heterogeneous structural and transcriptional signatures of pre-cancerous cystic lesions in the development of PDAC
Authors: Austin N. Southard-Smith, Reyka G. Jayasinghe, Andre L. Targino da Costa, Liang-I Kang, John M. Herndon, Jacqueline Mudd, Andrew Houston, Xiang Li, Michael C. Wendl, Faria A. Simin, Xiangwei Fang, Feng Chen, Koushik K. Das, Ryan C. Fields, Li Ding
Journal: Cancer Research (2025)

Abstract Pancreatic ductal adenocarcinoma PDAC has been observed to arise in the context of diverse pre-cancerous cystic (intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCNs)) and pre-cystic (pancreatic intraepithelial neoplasia (PanIN)) lesions in the clinic. While mouse models of PDAC and these precancerous lesions have existed for a decade, only recently has the transcriptional signature of dysplastic progression for one of these lesions (PanIN) been thoroughly characterized at single cell resolution. Utilizing a multimodal, spatial interrogation via Xenium and co-detection by indexing (CODEX) of PanIN (n=5), IPMNs (n=5), MCNs (n=2), and PDAC (n=5) at varying stages, we identify transcriptional signatures of each lesion at varying stages of progression and alterations of the pre-cancer microenvironment composition and structure. In doing so, we observed a conserved gastric metaplasia phenotype along the progression from PanIN to IPMN that is maintained in a subset of cells in higher grade and dual-subtype IPMNs. This phenotype is diminished in invasive PDAC. By contrast, MCN cyst epithelium and a small subset of PanIN cells lacked the expression of gastric markers and exhibited a more reactive ductal phenotype. Directly, adjacent to each of the pre-cancerous lesions we observed a thin layer of myCAF-like fibroblasts frequently interspersed with T cells that were otherwise excluded from the region surrounding invasive PDAC while the myCAF layer expanded. In the case of MCNs specifically this thin myCAF-like layer coincided with an ovarian-like expression signature alongside other markers. Our findings offer a high resolution window into the heterogeneity of PDAC precursor lesions, highlighting shared dysplastic expression and structural phenotypes along the progression towards invasive PDAC. Citation Format: Austin N. Southard-Smith, Reyka G. Jayasinghe, Andre L. Targino da Costa, Liang-I Kang, John M. Herndon, Jacqueline Mudd, Andrew Houston, Xiang Li, Michael C. Wendl, Faria A. Simin, Xiangwei Fang, Feng Chen, Koushik K. Das, Ryan C. Fields, Li Ding. Shared and heterogeneous structural and transcriptional signatures of pre-cancerous cystic lesions in the development of PDAC [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 761.