tbuckley/cabot-search huggingface dataset:
Abstract 3373: Event-free survival among polycythemia vera patients treated with novel JAK inhibitors: a comparative analysis using real-world genomic data and electronic health records
Authors: Stacy Charlerie, Nathan Lee, Jaime Smith, Angela X. Qu
Journal: Cancer Research (2025)

Abstract Known as a chronic myeloproliferative neoplasm, Polycythemia Vera (PV) is a rare blood cancer characterized by an abnormal increase in the number of red blood cells. PV is associated with increased risk of thrombotic events and mortality as well as other complications, including splenomegaly, macrovascular and microvascular events (e.g., transient ischemic attacks, erythromelalgia, ocular migraines), and aquagenic pruritus. The exact cause is unknown, but genetic mutations associated with a protein called Janus kinase 2 (JAK2) are often involved, and as such genomic testing is often part of the diagnostic journey and treatment options. Real-world data (RWD) and real-world evidence (RWE) have emerged as powerful tools for unlocking the potential of healthcare data generated in routine clinical practice. In oncology, RWD has been instrumental in multiple areas including 1) Discovering novel biomarkers by uncovering associations of genetic, molecular, and clinical outcomes that predict treatment response and disease progression; 2) Identifying comorbidities by recognizing coexisting conditions that may impact treatment outcomes and patient management 3) Optimizing treatment pathways by identifying effective treatment sequences and combinations for specific patient populations; 4) Enriching clinical trials by selecting the most appropriate patient populations for clinical trials and accelerating drug development. In this study, we aim to leverage electronic health records (EHR) data to conduct a comparative analysis of event-free survival (EFS) in PV patients on novel JAK inhibitor therapy versus other standard of care first-line treatments. By utilizing EHR data, we can identify key clinical factors associated with EFS and potentially develop predictive models to inform personalized treatment strategies. Additional exploration of real-world genetic/genomic data for insights to predict thrombotic events or mortality is forthcoming. This research has the potential to improve the management of PV patients and reduce the burden of disease. We will present our findings with some preliminary data, describe the data sources used, outline the technologies leveraged, and conclude with lessons learned. Citation Format: Stacy Charlerie, Nathan Lee, Jaime Smith, Angela X. Qu. Event-free survival among polycythemia vera patients treated with novel JAK inhibitors: a comparative analysis using real-world genomic data and electronic health records [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 3373.
Abstract 4323: CARM1-mediated methylation of ZNF703 regulates its oncogenic functions in estrogen receptor positive breast cancer
Authors: Jingjing Zhou, Eui-Jun Kim, Gui Ma, Ang Gao, Wei Xu
Journal: Cancer Research (2025)

Abstract ER-positive (ER+) breast cancer, characterized by estrogen receptor expression on tumor cells, constitutes approximately 70% of all breast cancer cases. Identifying specific oncogenes and elucidating relevant oncogenic mechanisms are critical for developing effective therapies. ZNF703, a NET/N1Z family transcription factor, drives 8p12 locus amplification found in 10-20% of ER+ breast tumors. ZNF703 has been reported as an oncogene that promotes ER+ breast tumorigenesis in vitro. However, its regulation and in vivo oncogenic function remain unclear. We showed that ZNF703 expression is induced by estradiol in ER+ cell lines. ShRNA-mediated ZNF703 knockdown significantly reduced cell proliferation in MCF7 and BT474 cells. ZNF703 is post-translationally modified, which may affect its nuclear localization as well as its functions. Using mass spectrometry, we identified two asymmetrically di-methylated arginine residues (R544 and R580) on ZNF703 in human breast tumors. Protein arginine (R) methylation is catalyzed by protein arginine methyltransferases (PRMTs), which are classified into Type I, II, and III based on the type of methyl-R they produced. Among these, CARM1, a Type I PRMT, catalyzes asymmetric di-methylation of arginine residues. We showed that ZNF703 is methylated by CARM1 in in vitro methyltransferase assay. Furthermore, ZNF703 protein levels were reduced in CARM1 knockout MCF7 cells, accompanied by an increased degradation rate, suggesting that ZNF703 may be stabilized by CARM1. Given the lack of an ER+ breast cancer mouse model, we derived an ER+ MG1 rat cell line from estrogen-induced rat breast tumors. Consistent with our findings in human ER+ cell lines, ZNF703 was validated as an estrogen-induced gene in MG1 cells. ZNF703 knockout in MG1 cells impaired cell proliferation and colony formation. Functional rescue experiments demonstrated that re-expression of wild-type ZNF703 fully restored cell growth, whereas the methylation-deficient mutants ZNF703 R580K and R544K only partially rescued the proliferation defect. Our results implicate that CARM1-mediated ZNF703 methylation may regulate its stability and oncogenic functions. Given that patients diagnosed with 8p12 locus amplification caused by ZNF703 typically have poor prognosis, our MG-1/ACI rat syngeneic model would enable the investigation of ZNF703’s oncogenic functions in vivo. Citation Format: Jingjing Zhou, Eui-Jun Kim, Gui Ma, Ang Gao, Wei Xu. CARM1-mediated methylation of ZNF703 regulates its oncogenic functions in estrogen receptor positive 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 4323.
Abstract 4037: Epigenetically-controlled CEBPB regulates kidney cancer tumorigenesis via GPD1L-mediated ether lipid synthesis
Authors: Thi Ha Nguyen, Xuan Linh Mai, Tin Tin Manh Nguyen, Hoonsik Nam, Sunghyouk Park, Ji Yun Lee
Journal: Cancer Research (2025)

Abstract The VHL-HIF axis has been recognized as a major regulator of lipid accumulation and tumorigenesis in clear cell renal cell carcinoma (ccRCC), but a growing number of VHL-HIF-independent pathways suggests possible alternative regulators. By screening epigenetic drivers and transcription factors, we identified CCAAT/enhancer-binding protein beta (CEBPB) as a key VHL-independent transcription factor crucial to lipid-related ccRCC progression, which was confirmed through in vitro/vivo experiments. CEBPB levels, regulated by H3K27ac and H3K4me, were also correlated with various poor prognostic factors in ccRCC patients. Mechanistically, CEBPB transcriptionally repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L), causing substrate (dihydroxyacetonephophate) accumulation for ether lipid synthesis. This enhanced Akt activation through membrane recruitment, and the subsequent downregulation of carnitine palmitoyltransferase 1A (CPT1A) led to lipid accumulation. Connecting multiple elements of the Hallmarks of Cancer in an unbranched path, the CEBPB-GPD1L-ether lipid-Akt-CPT1A axis is proposed as a new VHL-independent mechanism of lipid-related ccRCC tumorigenesis. Significance: The identification of CEBPB as a VHL-independent regulator of lipid metabolism and tumorigenesis shows how major cancer hallmarks (epigenetics, metabolites, and signaling) can be orchestrated by single factor. The proposed CEBPB-GPD1L-ether lipid-Akt-CPT1A axis provides new insights and therapeutic potentials for the regulation of lipid-related tumorigenesis in ccRCC Citation Format: Thi Ha Nguyen, Xuan Linh Mai, Tin Tin Manh Nguyen, Hoonsik Nam, Sunghyouk Park, Ji Yun Lee. Epigenetically-controlled CEBPB regulates kidney cancer tumorigenesis via GPD1L-mediated ether lipid synthesis [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 4037.
Abstract 1754: Evaluating the synergism between circadian clock compounds with chemoradiation against GBM
Authors: Priscilla Chan, Yoshiko Nagai, Qiulian Wu, Jiarui Wang, Theodore Kamenecka, Laura A. Solt, Jamie Cope, Tsuyoshi Hirota, Jeremy N. Rich, Steve A. Kay
Journal: Cancer Research (2025)

Abstract The circadian clock has been associated with numerous diseases and, in recent years, been linked to every known cancer hallmark. In the case of glioblastoma (GBM), high expression of positive regulators of the clock, such as Brain and Muscle ARNT-Like 1 (BMAL1), has been linked to shorter survival time while high expression of the negative regulators of the clock confers longer survival time. Furthermore, BMAL1 and Circadian Locomotor Output Cycles Kaput (CLOCK) were found to be essential for GBM stem cell (GSC) proliferation, stemness, and metabolism. GSCs are typically resistant to chemoradiation and secrete factors that drive neoangiogenesis and immune suppression in the tumor microenvironment (TME). However, we found that GSCs are specifically sensitive to genetic and pharmacological perturbation of these core clock components. Consequently, in this study, we sought to explore the anti-GBM effects of chemoradiation in combination with the novel Cryptochrome (CRY) stabilizer SHP1705, which inhibits BMAL1 and CLOCK transcriptional activity, and the novel REV-ERB agonist SR29065, which inhibits BMAL1 transcription. SHP1705 has proven to be safe and well-tolerated in Phase I clinical trials and SR29065 is well-tolerated in mice without evidence of cytotoxicity. Our findings highlight the potential of small molecule circadian clock modulating compounds as a novel treatment paradigm that sensitizes resistant GBM cell populations to chemoradiation. Citation Format: Priscilla Chan, Yoshiko Nagai, Qiulian Wu, Jiarui Wang, Theodore Kamenecka, Laura A. Solt, Jamie Cope, Tsuyoshi Hirota, Jeremy N. Rich, Steve A. Kay. Evaluating the synergism between circadian clock compounds with chemoradiation against GBM [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 1754.
Abstract 4156: Differential effects of tumor metabolites on T cell activation and effector function
Authors: Daniel Hua, Sadna Budhu, Anais Assouvie, Svena Verma, Mamadou Bah, Jedd D. Wolchok, Taha Merghoub
Journal: Cancer Research (2025)

Abstract Over the past decade, immunotherapies have significantly improved clinical outcomes in cancer patients. The FDA approval of ICB for cancer treatment represents a clinical milestone, however, durable responses are observed in only ∼20-40% of patients. The immunosuppressive nature of the tumor microenvironment (TME) presents a major challenge for effective anti-tumor responses. Tumor cells are highly metabolically active compared to other cells in the TME. Processes such as glycolysis and oxygen consumption (OXPHOS) lead to tumor hypoxia and the accumulation of metabolites in the TME. Metabolites found in the TME play key roles in immunosuppressive pathways including the adenosine-A2A receptor (A2AR) signaling pathway, and the Tryptophan-kynurenine-aryl hydrocarbon receptor (AHR) axis. Here we investigated how these metabolic pathways directly affect activation and effector function of T cells. In addition, we examined whether these pathways overlap functionally. To explore how TME metabolites affect T cell function, naïve mouse T cells were activated in the presence of metabolites including lactic acid (Lac), adenosine (Ado), kynurenine (Kyn). After 72 hours, T cells were analyzed via flow cytometry for proliferation and activation. We found that lactic acid decreased T cell frequencies and proliferation, but increased expression of CD39 and CD73, key enzymes involved in the conversion of ATP to Ado. Intriguingly, the combination of Kyn and Ado uniquely promoted T cell activation, showing markedly elevated expression of classical activation and effector markers such as CD44, CD25, and Granzyme B along with reduced CD39 and CD73 levels. Similar findings were observed in a clonogenic killing assay using tumor-specific T cells co-cultured with metabolites corroborating the functional relevance of our observations. Lactate negatively affected T cell killing function and the combination of Kyn and Ado showed the largest increase in killing efficiency. These findings suggest potential synergy between Kyn and Ado pathways in enhancing T cell function within the TME possibly through complementary pathways that bypass or counteract typical immunosuppressive signals. Further mechanistic investigation could unlock new strategies to overcome TME-induced immunosuppression and enhance existing immune based therapies. Citation Format: Daniel Hua, Sadna Budhu, Anais Assouvie, Svena Verma, Mamadou Bah, Jedd D. Wolchok, Taha Merghoub. Differential effects of tumor metabolites on T cell activation and effector function [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 4156.
Abstract 2023: AccuScan: an ultra-sensitive and robust MRD detection using WGS with single-read error correction
Authors: Xinxing Li, Lui Ng, George Yeung, Yingyu Wang, Paul Tang, Tobias Wittkop, Malek Faham, Li Weng, William Cho, None Dominic, Chi-chung Foo, Zhiqian Hu
Journal: Cancer Research (2025)

Abstract Whole-genome sequencing (WGS) of cell-free DNA (cfDNA) holds tremendous potential for detecting molecular residual disease (MRD), but its accuracy has been constrained by errors introduced during library preparation and sequencing. To overcome these limitations, we introduced AccuScan, a novel and robust cfDNA WGS technology that enables genome-wide error correction at the single-read level, achieving an error rate of 4.2 × 10-7, which is orders of magnitude improvement over conventional read-centric de-noising approaches. AccuScan has demonstrated analytical sensitivity down to parts per million (ppm) circulating variant allele frequency (cVAF), while maintaining 99% specificity at the sample level. By combining the convenience of WGS with the sensitivity and specificity of tumor-informed approaches, AccuScan enables precise detection of MRD in a timely manner, addressing critical unmet needs in colorectal cancer (CRC) adjuvant therapy decision-making. In the current clinical study involving 56 CRC patients who went through curative intended surgery (stages I: 7, 12.5%; stage II: 17, 30%; stage III: 26, 46.4%; stage IV: 6, 10.7% ), AccuScan achieved ∼88% sensitivity for MRD detection from a single sample collected within six weeks post-surgery. The test showed a strong correlation with recurrence risks over a three-year follow-up period while delivering 100% specificity. Notably, AccuScan captured MRD at &amp;lt;100 ppm cVAF, demonstrating its ultra-sensitive detection capabilities at the landmark timepoint when adjuvant therapy decisions need to be made. With a simple and distributable workflow, AccuScan demonstrated high performance and a high success rate in processing cfDNA samples across a broad range of input DNA quantities. Its current performance is powered by a straightforward statistical model that leverages single nucleotide variant (SNV) information. Future advancements in performance are anticipated with expanded cfDNA WGS datasets and the incorporation of cutting-edge machine learning strategies. Citation Format: Xinxing Li, Lui Ng, George Yeung, Yingyu Wang, Paul Tang, Tobias Wittkop, Malek Faham, Li Weng, William Cho, Dominic, Chi-chung Foo, Zhiqian Hu. AccuScan: an ultra-sensitive and robust MRD detection using WGS with single-read error correction [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 2023.
Abstract 4913: PREDICT Breast v4: Advancing equity in breast cancer prognosis for diverse populations
Authors: Yi-Wen Hsiao, Gordon C. Wishart, Paul D.P. Pharoah, Pei-Chen Peng
Journal: Cancer Research (2025)

Abstract Breast cancer, the most common cancer among women globally, remains a significant public health challenge. Prognosis, influenced by factors such as tumor characteristics, patient demographics, and treatment choices, is a major concern for patients. Tools like the PREDICT Breast v3 model (https://breast.v3.predict.cam/) help weigh treatment benefits against short- and long-term risks, enabling more personalised prognostic predictions. However, its performance disparities among non-Hispanic Black and non-Hispanic Asian patients in the US highlight the need for more equitable and inclusive tools. Therefore, this study aims to develop a breast cancer prognostic model that improves predictive accuracy across diverse populations and reduces disparities in prognostic outcomes. Here, we analysed data from 273, 918 breast cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database, each with clinical records and socioeconomic status (SES) information. The data were split 7:3 for model training and validation, with 10-fold cross-validation applied for parameter tuning. We first evaluated both conventional methods (PREDICT v3) and advanced machine learning models, including survival XGBoost, survival random forest, DeepHit, and DeepSurv, using calibration and discrimination as evaluation metrics. After comparing the models, we selected the DeepHit neural network as the best-performing approach due to its lowest calibration error and highest discrimination. We then examined whether incorporating SES improved performance by comparing SES-adjusted and unadjusted DeepHit models. Our results showed that the SES-adjusted DeepHit model achieved strong calibration (within 1.3% of observed deaths) and reduced racial disparities compared to PREDICT v3, which exhibited calibration errors of 30% for non-Hispanic Asians and 20% for non-Hispanic Blacks. These findings emphasise the importance of incorporating SES factors to enhance model accuracy and equity, underscoring the critical need for fairness in prognostic prediction. This work advances the application of machine learning in cancer prognosis and provides a foundation for addressing health disparities in clinical prediction tools. Citation Format: Yi-Wen Hsiao, Gordon C. Wishart, Paul D.P. Pharoah, Pei-Chen Peng. PREDICT Breast v4: Advancing equity in breast cancer prognosis for diverse populations [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 4913.
Abstract 1939: The potentiality of capillary electrophoresis as a novel detection method for circulating tumor cells
Authors: Tetsushi Yamamoto, Haruka Fukita, Risa Nishizawa, Kuniko Mitamura, Atsushi Taga
Journal: Cancer Research (2025)

Abstract Background: Circulating tumor cells (CTCs) are involved in metastasis, and detection of CTC has clinical utility as a biomarker for diagnosis of metastatic cancer patients. Therefore, detection of CTCs from blood is one of the most important approaches to identify metastatic cancer. However, the number of CTCs present in blood is considered less than a few hundred per mL of blood. Therefore, development of sensitive analytical method is required for CTC detection. We previously described a direct cell analysis method based on differences in cell surface charge using capillary electrophoresis (CE). In the present study, we investigate whether this analytical method can detect cancer cells in blood. Methods: We used the two human colorectal cancer cell lines (DLD-1 and SW480) and one pancreatic cancer cell line (BxPC-3), and blood sample from healthy donor as model samples. To prepare CTC model blood, cancer cells solution was added to blood sample. The stability of CTCs in blood was determined to analyze the model CTC samples after repetition of freeze-thawing. Capillary electrophoresis was performed at room temperature (ca. 25°C) using a linear polyacrylamide-coated fused silica capillary tube (50 cm × 75 μm i.d., effective length 9.5 cm), and 50 mM phosphate buffer (pH 6.8) was used as running buffer. The sample solution was introduced to the anodic end of the capillary with the hydrostatic introducing method (10 cm × 10 s). Results: Analysis of each sample revealed that peaks corresponding to cancer cells and blood cells were detected at different migration times. To clarify whether cancer cells in blood can be detected, we prepared CTC model blood by mixing cancer cell line and blood. We could successfully detect peaks corresponding to cancer cells in the blood separately from peaks corresponding to blood cells. These findings suggested that cancer cells can be distinguished from blood cells as cancer cell surfaces are more charged than blood cells. On the other hand, peak pattern of CTC model sample which repeated freeze-thawing was not different that of CTC model sample with non-freezing. This finding suggested that stored frozen blood samples might be useful for blood test to detect CTCs using this analytical method by CE. Conclusion: Therefore, direct cell analysis method using CE might be a potentially novel detection method for CTCs in blood. Citation Format: Tetsushi Yamamoto, Haruka Fukita, Risa Nishizawa, Kuniko Mitamura, Atsushi Taga. The potentiality of capillary electrophoresis as a novel detection method for circulating tumor 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 1939.