tbuckley/cabot-search huggingface dataset:
Abstract 3090: miRNA-221-5p-mediated epigenetic regulation promotes chemoresistance and offers therapeutic potential in ovarian cancer
Authors: Tasmin Rahman Omy, Naresh Sah, Mark Reedy, Ganesh Acharya, Komaraiah Palle
Journal: Cancer Research (2025)

Abstract Epithelial ovarian cancer (EOC) is a highly aggressive malignancy and the leading cause of gynecological cancer-related deaths. The majority of patients are diagnosed at advanced stages (III-IV), where treatment involves surgical debulking followed by platinum-based chemotherapy. While initial responses to therapy are often favorable, over 70% of advanced-stage EOC patients experience recurrence, typically accompanied by resistance to standard of care treatments. This chemoresistance significantly limits therapeutic success and worsens patient prognosis. Understanding the molecular mechanisms driving resistance is critical for developing effective therapeutic strategies. Emerging evidence highlights the role of miRNAs in regulating gene expression networks associated with DNA damage repair and chemoresistance. miRNA-221-5p has been implicated in modulating tumor progression and therapeutic responses in various cancers. Here, we investigate its role in ovarian cancer, focusing on regulating RAD18 and RAD51—key mediators of DNA damage tolerance and homologous recombination repair (HRR). Our analysis of miRNA expression in a panel of human ovarian cancer cell lines revealed low to undetectable levels of miRNA-221-5p, coupled with elevated expression of DNA damage response and repair genes such as RAD18 and RAD51. Our experimental data demonstrate that miRNA-221-5p regulates RAD18 and RAD51 transcripts through 3’-UTR, leading to their post-transcriptional repression and subsequent restoration of ovarian cancer cell sensitivity to platinum drugs. Mechanistically, our results confirm that miRNA-221-5p epigenetically regulates RAD18- and RAD51-mediated DNA damage tolerance and homologous recombination repair. Importantly, restoring miRNA-221-5p downregulates RAD18 and RAD51 and sensitizes chemoresistant ovarian cancer cells to platinum drugs, offering a promising strategy to enhance therapeutic outcomes. Overall, our data demonstrate that miRNA-221-5p is a critical regulator of chemotherapy-induced epigenetic and transcriptional alterations, making it a prospective therapeutic target for overcoming chemoresistance and avoiding EOC recurrence. Citation Format: Tasmin Rahman Omy, Naresh Sah, Mark Reedy, Ganesh Acharya, Komaraiah Palle. miRNA-221-5p-mediated epigenetic regulation promotes chemoresistance and offers therapeutic potential in 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 3090.
Abstract 5374: Metabolic reprogramming regulates tyrosine receptor kinase c-Met in prostate cancer
Authors: Songyeon Ahn, Tagari Samanta, Junhyoung Park, Benny A. Kaipparettu
Journal: Cancer Research (2025)

Mitochondrial metabolic reprogramming is known to regulate oncopathways. To understand mitochondria-regulated oncopathways in prostate cancer (PC), we used a transmitochondrial cybrid system. Under a benign prostate cell line PNT1a, cybrids were generated after cytoplasmic fusion from PNT1a (PNT1/PNT1) and PC cell line PC3 (PC3/PNT1). PC3/PNT1 cybrids showed increased tumor stemness, metastasis, and mitochondrial activity with enhanced OXPHOS and fatty acid oxidation (FAO) compared to PNT1/PNT1 cybrids. RNASeq analysis of cybrids identified increased mRNA expression of Mesenchymal Epithelial Transition receptor (c-Met) in cybrids with cancer mitochondria. c-Met is a receptor tyrosine kinase (RTK) and an essential receptor that regulates multiple cellular signaling and homeostasis in mammalian cells. c-Met is often over-expressed in several types of cancers and is thus considered a potential therapeutic target. c-Met activation is known to increase glucose metabolism by upregulating the expression of glycolysis-related genes such as GLUT-1, HK-2, PFK-1, LDH-1, and SIRT1 in tumor cells. However, how tumor metabolism affects c-Met expression is unclear. Etomoxir (FAO inhibitor) and Atovaquone (OXPHOS inhibitor) suppressed c-Met protein expression through the mTOR-P70S6K pathway in PC cells. Rapamycin (mTOR inhibitor) reduced c-Met expression in PC3 and DU145 PC cells. Preliminary analysis suggests that the mitochondrial inhibitors and capmatinib, an FDA-approved c-Met inhibitor, have a combinatorial effect. Collectively, this study suggests that mitochondrial metabolic reprogramming to FAO in PC upregulates c-Met activity. Citation Format: Songyeon Ahn, Tagari Samanta, Junhyoung Park, Benny A. Kaipparettu. Metabolic reprogramming regulates tyrosine receptor kinase c-Met 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 5374.
Abstract 6193: Population-level interventions to prevent alcohol-related cancers: A scoping review
Authors: Priyanka Basu, Jovan Julien, Sangeeta Goswami, Anton L.V. Avanceña
Journal: Cancer Research (2025)

Alcohol use and misuse are associated with at least eight types of alcohol-related cancers, namely cancers of the oral cavity, pharynx, larynx, esophagus (squamous cell carcinoma only), stomach, colon, liver (hepatocellular carcinoma only), and breast in females. Population-level interventions that reduce alcohol use may mitigate this cancer burden. This scoping review examines and synthesizes evidence on the effectiveness of these interventions on cancer-related outcomes. We followed the PRISMA-ScR guidelines and searched MEDLINE and Web of Science for English-language articles (1987 onwards) using keywords and terms related to interventions, alcohol use, and cancer in titles and abstracts. Only original quantitative research articles evaluating population-level interventions’ impact on cancer outcomes were included. Initial data extraction was conducted using Elicit, an AI-based research tool, which was reviewed by the research team for accuracy. Out of 1,531 studies, 68 full-texts were assessed for eligibility, and 35 were included in the final qualitative synthesis. Most studies were focused on Europe (N=17), Asia and Oceania (N=11), and North America (N=4). Study designs included randomized controlled trials (N=6), observational studies (N=18), and simulation models (N=11). The most common cancer-related outcome was cancer incidence (N=19), followed by cancer mortality (N=11) and knowledge/awareness of alcohol as a carcinogen (N=10). Primary prevention studies (N=31) focused on reducing alcohol-related cancers through educational or media initiatives (N= 13), adherence to clinical guidelines (N=11), and alcohol pricing policies (N=6) like alcohol taxes and minimum unit pricing. Five studies addressed secondary prevention via educational and clinical interventions like screening, health assessment, and treatment of alcohol misuse. No tertiary prevention studies were identified. This scoping review identified several gaps in our understanding of population-level interventions for alcohol-related cancers. Given the number of ever and current drinkers globally, additional studies are needed on secondary and tertiary prevention strategies. Few studies evaluated alcohol pricing policies despite the long-standing evidence supporting its effectiveness in reducing alcohol use. Meeting cancer prevention guidelines may reduce cancer incidence and mortality, and future research should focus on the most effective and cost-effective ways of translating recommendations into interventions in real-world contexts. Citation Format: Priyanka Basu, Jovan Julien, Sangeeta Goswami, Anton L.V. Avanceña. Population-level interventions to prevent alcohol-related cancers: A scoping review [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 6193.
Abstract 2440: Correlation analysis between AI-based H-score and clinical data in MET IHC stained WSIs
Authors: Hyeon Seok Yang, Yunseob Hwang, DoKyung Kim, Yoon-La Choi, Kyungsoo Jung, Minjung Sung, Young Kee Shin, Ji-Hye Nam, Tae-Yeong Kwak, Sun Woo Kim, Hyeyoon Chang
Journal: Cancer Research (2025)

Abstract Background: MET protein expression is considered a potential biomarker in lung cancer, but there is no guideline for analysis, and its clinical significance has not been sufficiently analyzed. In order to explore its potential as a biomarker, it is necessary to analyze the relationship between the expression level of the biomarker and clinical data. In this study, we analyze the relationship between H-score, which is automatically measured based on cell detection detected by a deep learning model, and clinical data. Design: The dataset included 270 whole slide images (WSIs) of non-small cell lung cancer (NSCLC) immunohistochemically stained with a MET antibody (SP44), obtained through resection, biopsy, or endobronchial ultrasound (EBUS). For each of these WSIs, pathologists estimated the proportions for 0, 1+, 2+, and 3+ according to duty, and calculated the H-score based on these values. In addition, the analysis areas were manually specified to exclude the internal controls. We developed analysis models based on deep learning. The cancer area localization model identified the cancer areas for each patch, and the cell analysis model identified the cell membrane, cytoplasm, and nucleus of each cell. Additionally, the MET expression intensity of each cell was classified as 0, 1+, 2+, and 3+ based on the mean diaminobenzidine (DAB) optical density (OD) measured in the cell membrane. The H-score was calculated accordingly. Result: For each WSI, the correlation between the H-score estimated by AI and the pathologist's H-score was calculated as Pearson’s correlation coefficient = 0.6909 (p&amp;lt;0.0001). In addition, when analyzing the H-score estimated by AI by tumor subtype of clinical data, the mean H-score of adenocarcinoma samples was estimated to be 177, which was significantly higher than the mean H-score of 116 estimated for squamous cell carcinoma samples (Mann-Whitney test, p &amp;lt; 0.0001). Conclusion: For MET IHC stained WSIs, H-scores were estimated through cell analysis using deep learning and image analysis, and the correlation with pathologist's H-scores was confirmed, and H-score differences between tumor subtypes were confirmed. Semi-automated AI analysis can be used to analyze the correlation between clinical data and MET staining expression. Citation Format: Hyeon Seok Yang, Yunseob Hwang, DoKyung Kim, Yoon-La Choi, Kyungsoo Jung, Minjung Sung, Young Kee Shin, Ji-Hye Nam, Tae-Yeong Kwak, Sun Woo Kim, Hyeyoon Chang. Correlation analysis between AI-based H-score and clinical data in MET IHC stained WSIs [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 2440.
Abstract 2793: LncRNA CRNDE facilitates head and neck cancer progression by modulating the tsmiRs-oncogenes network regulating multiple oncogenic signaling pathways
Authors: Ting Jui Lin, Ann Joy Cheng, Yin Ju Chen, Hung Hang Huang
Journal: Cancer Research (2025)

Abstract Recent studies have emphasized the pivotal role of long non-coding RNAs (lncRNAs) in tumorigenesis, with CRNDE identified as dysregulated in several cancers. This study explores the role of CRNDE in head and neck cancer (HNC), a globally prevalent malignancy. We demonstrate that CRNDE drives key malignant phenotypes in HNC, including enhanced cell migration, invasion, proliferation, and chemoresistance. RNA sequencing identified numerous downstream effectors, with 195 oncogenes significantly enriched in cancer-related pathways, such as focal adhesion, actin cytoskeleton organization, and PI3K-AKT, Ras, and Rap1 signaling. To elucidate the regulatory mechanisms of CRNDE, we observed that it predominantly localizes in the cytosol of HNC cells, suggesting its primary role in miRNA modulation. Bioinformatic analysis identified 14 miRNAs with strong regulatory potential. Among these, three tumor-suppressive miRNAs (TsmiRs)—miR-181c-5p, miR-29a-3p, and miR-29b-3p—were prioritized based on their clinical relevance from the TCGA-HNSC dataset. Further analysis revealed that these miRNAs potentially regulate 391, 417, and 137 target genes. Integrative analysis demonstrated that these hub miRNAs co-regulate 69 oncogenes, significantly influencing five cancer-related pathways. We constructed a comprehensive CRNDE-TsmiRs-Oncogenes regulatory network, uncovering a complex cross-regulatory mechanism. Moreover, we validated the CRNDE-miR-181c-PI3K/AKT3 axis as a critical pathway in HNC progression. Overexpression of miR-181c-5p markedly suppressed CRNDE-driven cancer progression by downregulating PI3K/AKT expression and mitigating malignant phenotypes, including migration, invasion, and chemoresistance. This study presents a novel CRNDE-TsmiRs-Oncogenes molecular network and highlights the CRNDE/miR-181c-5p/AKT axis as a promising biomarker and therapeutic target for improved HNC management. Citation Format: Ting Jui Lin, Ann Joy Cheng, Yin Ju Chen, Hung Hang Huang. LncRNA CRNDE facilitates head and neck cancer progression by modulating the tsmiRs-oncogenes network regulating multiple oncogenic signaling pathways [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 2793.
Abstract 1309: Decellularized extracellular matrix hydrogel for esophageal cancer model
Authors: Yunqing Kevin Kang
Journal: Cancer Research (2025)

Abstract Esophageal cancer is currently the sixth most common cancer worldwide and one of the most lethal cancers. The lack of physiologically relevant human esophageal cancer models has hindered the progress of developing effective strategies against esophageal cancer. To address the issue, we developed a decellularized esophageal matrix derived hydrogel. We then characterized the physicochemical properties of the decellularized extracellular matrix (dECM) hydrogel. To bioengineer the cancer model using the dECM hydrogel, we seeded esophageal squamous cell carcinoma KYSE30 on the dECM hydrogel and in the dECM hydrogel. They grew well and spread out in/on the dECM hydrogel. We also casted KYSE30-laden dECM hydrogel on a side of a well to see if KYSE30 will migrate out of the hydrogel. After culturing 3 days, we found that KYSE30 cells grew and started to migrate out of the dECM hydrogel, and migrated more after day 5. We counted the number of migrated cells. We found that cell migrated more at day 5. We then quantified cell proliferation of KYSE30 in the dECM hydrogel. We found that KYSE30 cells proliferated in the dECM hydrogel with time. These findings bring new potential to using the decellularized matrix derived hydrogel for future experiments in studying cancer behavior and practical applications for esophageal cancer models. Citation Format: Yunqing Kevin Kang. Decellularized extracellular matrix hydrogel for esophageal 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 1309.
Abstract 5986: Lurbinectedin/Irinotecan as a new therapeutic combination for small cell lung cancer
Authors: Miguel Ruiz Torres, Santiago Ponce, Juan Manuel Coya, Reyes Bernabe, Jon Zugazagoitia, Alvaro Ucero, Javier Baena, Luis Paz-Ares, Irene Ferrer
Journal: Cancer Research (2025)

Abstract Small Cell Lung Cancer (SCLC) is one of the most frequent and deadliest types of Cancer, with an overal survival (OS) of less than 14 months and a 2- year survival rate not exceeding 7%. Potentially targetable molecular alterations in kinase genes are uncommon in SCLC, and consequently, treatment has barely changed in the last fifty years. Irinotecan, a Topoisomerase II inhibitor, and Lurbinectedin, an inhibitor of transcription, are the two only recently approved chemotherapy agents employed as monotherapy in second line of treatment. Our group has led a Clinical Trial to test the efficacy of the combination of these two drugs in SCLC in patients previously treated with the standard of care. The Clinical trial shows a consistent reduction in tumor size and a significant improvement in the Progression-free survival (PFS) of patients. To determine the mechanisms behind this promising effect, we have conducted a series of experiments using our platform of Patient-Derived models (Patient Derived Xenografts (PDX), Circulating tumor Cell-Derived Xenografts (CDX) and PDX/CDX-derived organoids/spheroids). Treating our PDX/CDX models faithfully recapitulates the results observed in patients, with a clear increase in survival in mice treated with the combination. Short term treatment of PDX models, as well as 3D cultures of organoids (PDXDO) and spheroids (CDXDS) and 2D cultures of SCLC cell lines, helped us determine that the treatment causes elevated levels of DNA Damage, a blockade in DNA Replication, and finally apoptosis. The results from this study highlight the relevance of the combination of these two already approved drugs in the treatment of SCLC. Citation Format: Miguel Ruiz Torres, Santiago Ponce, Juan Manuel Coya, Reyes Bernabe, Jon Zugazagoitia, Alvaro Ucero, Javier Baena, Luis Paz-Ares, Irene Ferrer. Lurbinectedin/Irinotecan as a new therapeutic combination for 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 5986.
Abstract 2757: Hypermethylation of FAT4 linked to tumor progression in colorectal adenocarcinoma
Authors: Dalma Muller, Balazs Gyorffy
Journal: Cancer Research (2025)

Abstract Introduction: The gene FAT4 encodes a cell adhesion molecule of the protocadherin family. FAT4 can be linked to cancer progression at multiple levels, including metastasis, autophagy, epithelial-to-mesenchymal-transition, and as a tumor suppressor. Aberrant methylation, a common hallmark of colorectal adenocarcinoma, disrupts normal gene regulation. Purpose: We explored the methylation changes of FAT4 during colorectal cancer progression, using a large patient cohort with methylation microarray data. Methods: Raw data files of a collection of 2,356 colorectal tumor, adenoma, and normal samples from two microarray platforms (Illumina HM450K and EPIC) were processed in R using the minfi and the watermelon libraries. Based on a matrix of β-values, methylated regions and CpG loci were identified using Kruskal-Wallis-test complemented with ROC analysis. For data visualization we employed www.epigenplot.com, a web platform established based on our database. False discovery rate was set at 10%. Results: Based on UCSC RefGene data, 18 of the HM450K and 27 of the EPIC array probes were assigned to the FAT4 gene. All the probes hypermethylated in adenocarcinoma tissues compared to normal ones belonged to the CpG island chr4:126235895-126238930 of the proximal promoter region. When comparing to normal tissues, the TSS200 region had the most prominent hypermethylation (HM450K Δβ =0.28, AUC 0.9; EPIC Δβ = 0.22, AUC 0.85, p &amp;lt;0.0001), while the probes of the open sea CpGs in the protein coding region have shown a slight hypomethylation (HM450K Δβ = 0.1; EPIC Δβ = 0.14, p &amp;lt;0.0001). These changes were also present in adenoma tissues compared to normal ones. Based on KEGG classification, three other genes associated to the mTOR signaling pathway were similarly hypermethylated in the TSS200 region (Δβ &amp;gt;= 0.2), including WNT2, FZD10, and WNT7A. Conclusions: FAT4, a tumor suppressor gene with previously reported downregulation in CRC, shows significant hypermethylation in colon cancer, including the precursor lesions. Our results suggest that detection of these methylation changes in the promoter region of FAT4 might be utilized as a prognostic biomarker and in the early detection of CRC. Citation Format: Dalma Muller, Balazs Gyorffy. Hypermethylation of FAT4 linked to tumor progression in colorectal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2757.
Abstract 2826: Celastrol-Cu nanoparticles induce self-amplified cuproptosis augmented cancer immunotherapy
Authors: Huawei Pan, Liuxian Meng, Yifan Li, Tj (Tiejun) Bing
Journal: Cancer Research (2025)

Abstract Cuproptosis, a recently identified copper-dependent programmed cell death pathway, has emerged as a promising strategy in cancer therapy. Its effectiveness is closely linked to intracellular copper accumulation but is mitigated by elevated levels of glutathione (GSH) in tumor cells. A significant barrier to its clinical application lies in the challenge of facilitating the cellular uptake of copper ions. Additionally, intracellular copper ions rapidly bind with GSH, further complicating the induction of tumor cell death. Notably, no existing ionophore drug simultaneously acts as both a copper ionophore and a GSH scavenger to effectively induce cuproptosis. In summary, we have developed a celastrol-based nanomedicine that, upon complexation with copper ions, effectively promotes cuproptosis in a self-amplifying manner, as validated in both 4T1 subcutaneous and metastatic breast cancer models. This Cel-Cu NP platform provides a novel option with significant translational potential for the integrated programmed therapy of triple-negative breast cancer (TNBC) in immunologically “cold” tumors. Citation Format: Huawei Pan, Liuxian Meng, Yifan Li, Tj (Tiejun) Bing. Celastrol-Cu nanoparticles induce self-amplified cuproptosis augmented cancer immunotherapy [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 2826.