tbuckley/cabot-search huggingface dataset:
Abstract 3452: Investigating the relationship between obesity-related dyslipidemia, inflammatory myeloid cells, and cancer
Authors: Maria D. Sanchez-Pino, Ramesh Thylur Puttalingaiah, Dorota Wyczechowska, Timothy Kayes, Julia Panov, Jone Garai, Timothy Foster, Jovanny Zabaleta
Journal: Cancer Research (2025)

Abstract Background: Since people with obesity generally have altered immune responses, a high level of cholesterol, and a higher risk for cancer development and progression, it is important to investigate the relationship between cholesterol, immune cells, and cancer. The current study aims to assess the contribution of obesity-related excess lipids in priming subset of myeloid cells. Methods: The carcinogen diethylnitrosamine (DEN) was used to induce hepatocellular carcinoma (HCC) in mice (Wild-type and liver-specific Alb-CPT1-Knockout) and diet-induced obesity (DIO) was induced to evaluate the impact of obesity compared to lean mice. Tumor burden and transcriptomic profiling were performed. In vitro exposure to immature myeloid cells (IMCs) from mice bone marrow with LDL-cholesterol (LDLc) was performed for molecular (protein, RNAseq, ATACseq) assessments and functionality. Results: Obesity induced by diet increased the tumor burden on mice associated with steatosis and accumulation of myeloid-derived suppressor cells in the liver identified by flow cytometry. CPT1-KO mice showed increased gene expression of markers for immunosuppressive neutrophilic subtype and macrophages. Among different pathways, differentially expressed genes were involved in the MET and TGFb Signaling- ECM Remodeling &amp; Metastasis, Inflammation and Epigenetic &amp; Transcriptional Regulation. LDLc in vitro stimulation of IMCs increased the expression of immunosuppressive markers. Integration of RNAseq-ATACseq suggests that lipid-exposed IMCs have an epigenetically regulated activation program. Conclusion: Excess lipids facilitate liver cancer where inflammatory neutrophilic cells and macrophages may play a major contributing role. Funding: Pennington Research Center NORC U54-GM104940 and LSU LCMC Health Cancer Center. Citation Format: Maria D. Sanchez-Pino, Ramesh Thylur Puttalingaiah, Dorota Wyczechowska, Timothy Kayes, Julia Panov, Jone Garai, Timothy Foster, Jovanny Zabaleta. Investigating the relationship between obesity-related dyslipidemia, inflammatory myeloid cells, and 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 3452.
Abstract 969: Deciphering sex differences in clear cell renal cell carcinoma at the single-cell resolution
Authors: Xiangwei Fang, Yize Li, Xiyi Wei, Siqi Chen, Chia-Kuei Mo, Wagma Caravan, Preet Lal, Ruiyang Liu, Ilya Strunilin, Yizhe Song, Yuwei Zhang, Song Cao, Cody Weimholt, Feng Chen, Li Ding
Journal: Cancer Research (2025)

Abstract Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, accounting for approximately 70% of cases. Strikingly, ccRCC exhibits a marked sex disparity in prevalence, being significantly more common in men than women. This disparity underscores the importance of systematically investigating sex differences to elucidate their implications for the diagnosis, prognosis, and therapeutic strategies of ccRCC. To address this, we generated a comprehensive single-nucleus sequencing atlas (snRNA-seq and snATAC-seq) comprising over 400, 000 nuclei from 65 ccRCC cases. This dataset was complemented by paired bulk proteogenomic data, enabling a multi-layered analysis of the molecular landscape. The study cohort, including 21 females and 44 males, reflects the sex distribution observed in ccRCC incidence within the general population. Our analysis uncovered sex-associated molecular differences in key pathways driving ccRCC progression. These include genes regulating the hypoxia-inducible factor (HIF) pathway, a hallmark of ccRCC, as well as lipid metabolism and energy homeostasis pathways, which are critical to ccRCC progression. Furthermore, genomic characterization revealed significant sex differences in tumor mutational burden (TMB) and specific genetic alterations, including higher mutation frequencies in KDM5C and MTOR in male tumors. These genetic differences were linked to distinct downstream effects, suggesting sex-specific impacts on tumor biology. These findings illuminate new opportunities for developing sex-informed therapeutic strategies and biomarkers, enabling a more precise and tailored approach to ccRCC screening and treatment. Citation Format: Xiangwei Fang, Yize Li, Xiyi Wei, Siqi Chen, Chia-Kuei Mo, Wagma Caravan, Preet Lal, Ruiyang Liu, Ilya Strunilin, Yizhe Song, Yuwei Zhang, Song Cao, Cody Weimholt, Feng Chen, Li Ding. Deciphering sex differences in clear cell renal cell carcinoma at the single-cell resolution [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 969.
Abstract 7: Lipid-driven oxidative phosphorylation fuels lymph node colonization by esophageal tumor cells
Authors: Shanshan Li, Baifeng Zhang, Cuicui Huang, Yuying Zhao, Stephanie Ma, Xinyuan Guan
Journal: Cancer Research (2025)

Abstract Lymph node (LN) metastasis is a pivotal step in the progression of esophageal squamous cell carcinoma (ESCC) and is associated with poor clinical outcomes. Despite its significance, the mechanisms underlying the early colonization of LNs by tumor cells remain insufficiently understood. In this study, we utilized a human xenograft model of spontaneous LN metastasis and performed single-cell RNA sequencing to analyze the transcriptomes of tumor cells from primary tumors and LN metastases. A rare subset of metastasis-initiating cells (MICs) with stem-like characteristics was identified as critical drivers of LN metastasis. These MICs exhibited a unique metabolic adaptation, relying on fatty acid oxidation (FAO)-driven oxidative phosphorylation (OXPHOS) to survive in the lipid-enriched LN microenvironment. Additionally, nuclear factor erythroid 2-related factor 2 (NRF2) was found to play a key role in maintaining redox balance and supporting the metabolic resilience of MICs during metastatic progression. This study underscores the importance of FAO-driven OXPHOS and NRF2-regulated redox homeostasis in LN metastasis and highlights these pathways as promising targets for therapeutic intervention in ESCC. Citation Format: Shanshan Li, Baifeng Zhang, Cuicui Huang, Yuying Zhao, Stephanie Ma, Xinyuan Guan. Lipid-driven oxidative phosphorylation fuels lymph node colonization by esophageal 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 7.
Abstract 3344: The 31-gene expression profile identifies patients at risk of developing early distant metastases and can guide risk-appropriate surveillance strategies
Authors: Merve Hasanov, Elshad Hasanov, David Pariser, Sonia Morgan-Linnell, Samuel Dierks, Brian Martin, Abel Jarell
Journal: Cancer Research (2025)

Abstract Introduction: Up to 20% of patients with stage I-II cutaneous melanoma (CM) will develop distant metastases (DMs), with the most frequent DM sites being the liver, lungs, bone, and brain. Although patients who develop DM have poor prognosis, trials of new immunotherapies in patients with DM have reported 5-year survival rates as high as 50%. Critically, early detection of DM, when tumor burden is lower, tends to lead to better treatment responses. Thus, it is important to identify patients at the highest risk of developing DM so clinicians can recommend risk-appropriate surveillance and treatment plans. We previously assessed the ability of the 31-gene expression profile (31-GEP) to predict CNS metastases, and here we expand our analysis to assess 31-GEP risk prediction for DMs to the lung, liver, and bone. Methods: We conducted a retrospective analysis of patients with stage I-II CM clinically tested with the 31-GEP from 2013-2017 (n=1, 661). Differences in DM rates between groups were assessed with Chi-squared test. Survival estimates (DM-free survival, DMFS) were estimated using Kaplan-Meier and compared using the log-rank test. (*, p&amp;lt;0.05; **, p&amp;lt;0.001). Results: Among patients with stage I-II CM, a total of 90 DMs developed in 67 (4.0%) patients to the liver (n=48), lung (n=22), and/or bone (n=20). A higher percentage of patients with Class 2B than Class 1A developed DM to the liver (7.4% vs. 1.2%, **), lung (4.5% vs. 0.6%, **), and bone (3.0% vs. 0.8%, *). A 31-GEP Class 2B result was associated with significantly lower 5-year DMFS than Class 1B/2A or Class 1A for liver (91.7%, 92.2%, vs. 98.9%, **), lung (95.0%, 97.6%, vs. 99.4%, **), and bone (96.4%, 98.0%, vs. 99.2%, *). Of those with DM, the median time to develop DM (Class 1A, 1B/2A, vs. 2B) was 2.43, 2.22, vs. 2.27 years for liver; 1.74, 3.20, vs. 1.10 years for lung; and 3.2, 2.05, vs. 1.30 years for bone. Conclusion: Among patients with stage I-II CM, a greater percentage of those with a Class 2B 31-GEP developed DM at all studied sites, and 5-year DMFS was significantly lower for those with a Class 2B result. Thus, including 31-GEP testing with AJCC staging can allow clinicians to identify patients at higher risk of DM and recommend risk-appropriate surveillance modalities and frequency for early detection and treatment of DM. Citation Format: Merve Hasanov, Elshad Hasanov, David Pariser, Sonia Morgan-Linnell, Samuel Dierks, Brian Martin, Abel Jarell. The 31-gene expression profile identifies patients at risk of developing early distant metastases and can guide risk-appropriate surveillance strategies [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 3344.
Abstract 1028: Evaluating amplitude modulated radiofrequency electromagnetic fields as a cancer screening modality
Authors: Callum T. McGrath, Hugo Jimenez, Boris C. Pasche
Journal: Cancer Research (2025)

Abstract Background: Tumor-specific Amplitude Modulation Radiofrequency Electromagnetic Fields (AM RF EMF) have been identified in over 15 different tumor types. Tumor specific frequencies were identified by exposing patients with a known diagnosis of cancer to an AM RF EMF frequency sweep ranging from 0.1 Hz to 150 kHz. Frequencies that elicited an increase in pulse amplitude were registered as tumor-specific frequencies. We hypothesized that this mechanism could be used to screen for cancer, in which patients with an unknown diagnosis are exposed to previously identified tumor-specific frequencies and monitored for any change in hemodynamics. Methods: 17 patients with biopsy-proven hepatocellular carcinoma (HCC), 14 patients with biopsy-proven breast cancer (BC), and 31 healthy controls were recruited for the study and had their systolic blood pressure (sBP), diastolic blood pressure (dBP), pulse pressure (PP), cardiac output (CO), heart rate (HR) R-R interval (RRI), stroke volume (SV), and total peripheral resistance (TPR) measured while exposed to random (non-tumor-specific) AM RF EMF, HCC-specific AM RF EMF, and BC-specific AM RF EMF. Patient data was then used to train a one-dimensional convolutional neural network (1D CNN) to classify each dataset as control, HCC, or BC. Results: Overall accuracy for the model was 81.17%. AUC for the ROC curve for control, HCC, and BC was 0.91, 0.96, and 0.96 respectively. Conclusion: Our model demonstrates that AM RF EMF has the potential to be used as a cancer screening modality. Further studies will need to be performed with larger cohorts to validate the findings of this study and to improve the accuracy of the model. Additionally, future studies should investigate the potential for AM RF EMF-based screening for pancreatic cancer, as tumor-specific frequencies have previously been identified for the malady. Citation Format: Callum T. McGrath, Hugo Jimenez, Boris C. Pasche. Evaluating amplitude modulated radiofrequency electromagnetic fields as a cancer screening modality [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 1028.
Abstract 3066: Fumarylacetoacetate hydrolase (FAH) stimulates resistance to CDK4/6 inhibitors in hormone receptor-positive breast cancer via a novel non-canonical function
Authors: Jenny Hogstrom, Boryana Petrova, Hanna Doh, Camila Perea, Su Min Hong, Nina Kozlova, Kayla Cruz, Conor L. Evans, Jonah Lee, John Clohessy, Gerburg Wulf, Laura Collins, Naama Kanarek, Taru Muranen
Journal: Cancer Research (2025)

Abstract Breast cancer is the most prevalent cancer among women worldwide with hormone receptor-positive (HR+) cancer constituting 70% of all breast cancers. HR+ breast cancer patients are usually treated with targeted therapies, which include hormone therapy, as well as CDK4/6- and PI3K-inhibitors. Unfortunately, the tumors usually become resistant over time. In addition to genetic drivers of resistance, metabolic perturbations and enhanced activity of metabolic enzymes can also contribute to tumor growth, resistance and poor survival. We have discovered that Fumarylacetoacetate hydrolase (FAH), the last enzyme in tyrosine catabolism pathway, is enriched in HR+ breast tumors and correlates with poor survival. By using HR+ patient-derived organoid cultures (PDOs), we show that FAH stimulates resistance to multiple standard-of-care therapies. Despite its canonical function in tyrosine catabolism, FAH overexpressing cells do not preferentially utilize the tyrosine catabolism pathway. Instead, we surprisingly observe increased nuclear localization of FAH in patients treated with endocrine therapy and/or CDK4/6-inhibitors. Similarly, ER degraders and CDK4/6-inhibitors increase the ratio of nuclear FAH in patient-derived organoids, suggesting that the nuclear localization could drive resistance. To investigate this, we cloned a nuclear localization signal (NLS) to FAH and observed that FAH-NLS expressing PDOs were more resistant to CDK4/6-inhibitors. In contrast, blocking the nuclear translocation reversed the FAH-mediated resistance, showing that the nuclear localization is essential for the resistance phenotype. Collectively this suggests a yet uncharacterized moonlighting function of FAH in the nucleus and links this metabolic enzyme to treatment resistance in HR+ breast cancer. Citation Format: Jenny Hogstrom, Boryana Petrova, Hanna Doh, Camila Perea, Su Min Hong, Nina Kozlova, Kayla Cruz, Conor L. Evans, Jonah Lee, John Clohessy, Gerburg Wulf, Laura Collins, Naama Kanarek, Taru Muranen. Fumarylacetoacetate hydrolase (FAH) stimulates resistance to CDK4/6 inhibitors in hormone receptor-positive breast cancer via a novel non-canonical 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 3066.
Abstract 105: Netrin-1 activates Yap1 to promote pancreatic cancer metastasis and mutant Kras-independence
Authors: Chris R. Harris, Muhammad Sadeqi Nezhad, Shubhrika Jain, Wade Narrow, Darren R. Carpizo
Journal: Cancer Research (2025)

Abstract Although pancreatic ductal adenocarcinoma (PDAC) is only the 10th most common cancer, it is the 3rd leading cause of cancer deaths due to its high incidence of metastasis. In patient samples, PDAC metastasis associates with expression of the secreted protein Netrin-1, and indeed metastasis of pancreatic adenocarcinomas in mouse models is sharply reduced upon genetic or pharmacological ablation of Ntn1 signaling. Upon binding to its Unc5b receptor, Ntn1 activates the survival factor Yap1, which then promotes resistance to anoikis, which is a key trait of metastatic tumors. But metastatic PDACs are not the only expressers of Ntn1: indeed, primary pancreatic tumors can also derepress Ntn1 if selected to grow in the absence of mutant Kras. These Krasmut-independent tumors become dependent upon activation of Yap1 by Ntn1/Unc5b signaling, and suggest that patients with pancreatic cancer may benefit from combined pharmacological targeting of mutant Kras and Ntn1. Citation Format: Chris R. Harris, Muhammad Sadeqi Nezhad, Shubhrika Jain, Wade Narrow, Darren R. Carpizo. Netrin-1 activates Yap1 to promote pancreatic cancer metastasis and mutant Kras-independence [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 105.
Abstract 3393: A pan-cancer analysis of cancer-predisposition germline pathogenic variants (gPVs) utilizing the cancer genome atlas (TCGA) reveals distinct survival trends associated with immune response pathways
Authors: Alan Shen, Lin Li, Joshua Arbesman, Ying Ni, Pauline Funchain
Journal: Cancer Research (2025)

Abstract A family history of cancer has previously been shown to positively impact survival outcomes in various cancers. Additionally, specific cancer-predisposition germline pathogenic variants (gPVs) have also been shown to have a beneficial effect on survival across multiple cancers including colorectal cancer, ovarian cancer and melanoma. However, the impact on survival of commonly accepted cancer-predisposition gPVs across cancers has not been widely studied. Here, we examine the effect of 85 common cancer-predisposition gPVs on survival outcomes across all cancer types in the Cancer Genome Atlas (TCGA). When examining survival trends, we observed that cancers with a greater proportion of gPVs generally had improved survival (p = 0.0088). When examining each cancer indication separately, those with significantly improved survival amongst gPV positive patients included bladder [HR = 0.35, p = 0.01] and ovarian cancer [HR = 0.55, p = 0.0003], whereas head and neck squamous cell carcinoma had significantly worse survival [HR = 1.43, p = 0.04]. Interestingly, bladder and ovarian cancer gPV positive patients had significant upregulations in immune-stimulatory transcriptomic pathways with the majority of gPVs in the homologous recombination deficient (HRD) variant category, whereas the opposite was observed in head and neck squamous cell carcinoma. Thus, by examining a large array of cancer-predisposition gPVs in all cancer subtypes included in TCGA, we not only demonstrate the prevalence of a wider variety of gPVs across cancer indications but that specific categories of gPVs can influence survival across cancers in a beneficial manner, potentially by creating a pro-inflammatory immune response. Citation Format: Alan Shen, Lin Li, Joshua Arbesman, Ying Ni, Pauline Funchain. A pan-cancer analysis of cancer-predisposition germline pathogenic variants (gPVs) utilizing the cancer genome atlas (TCGA) reveals distinct survival trends associated with immune response 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 3393.
Abstract 2878: Preclinical characterization of GLR1061, a B7H3-targeted ADC with a novel DNA topoisomerase I inhibitor, demonstrated superior bystander effect to overcome tumor heterogeneity
Authors: Jiao Jiao, Yingjie Sun, Jiaxing Wang, Menghan Cui, Siyao Li, Wenjie Shao, Hairui Yuan, Haitong Sheng
Journal: Cancer Research (2025)

Abstract B7H3 (CD276) belongs to the B7 superfamily of immune checkpoint molecules. It is present at low levels in most normal tissues but is overexpressed in a variety of cancers, such as lung cancer, prostate cancer, breast cancer, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma. Notably, B7H3 overexpression has been found to be associated with a poor prognosis in a broad spectrum of malignant tumors, and it has become an attractive target for cancer therapy in recent years. B7H3-targeted antibody-drug conjugates (ADCs), such as DS7300, have shown positive clinical efficacy in small cell lung cancer, squamous non-small cell lung cancer, metastatic castration-resistant prostate cancer. GLR1061 is a B7H3 targeting ADC comprised of a humanized IgG1 monoclonal antibody, a cleavable linker and a novel DNA topoisomerase I inhibitor. Our independently developed topoisomerase I inhibitor had super strong cancer cell inhibition activity, which was 5 to 10 times stronger than DXd, and enhanced key advantages such as ADC bystander effect. Conjugated with B7-H3 antibody, which had superior binding and internalization, GLR1061 demonstrated more significant anti-tumor efficacy across various cancer types than DS7300 both in vitro and in vivo. In addition, in the CDX model of co-culture of antigen-positive and antigen-negative cells, GLR1061 exhibited much stronger bystander activity than DS7300, which was expected to overcome tumor heterogeneity and effectively eliminate cancer cells with different antigens expressions. In plasma stability studies, GLR1061 showed significantly lower free-payload release than DS7300 in different species (PBS, rat, monkey, and human). In a preclinical repeated-dose toxicology study in mice, GLR1061 showed good tolerability and reversible toxicity. Overall, GLR1061 demonstrated excellent specificity, efficacy, and safety as a next-generation therapy for the treatment of B7H3-positive tumors. Citation Format: Jiao Jiao, Yingjie Sun, Jiaxing Wang, Menghan Cui, Siyao Li, Wenjie Shao, Hairui Yuan, Haitong Sheng. Preclinical characterization of GLR1061, a B7H3-targeted ADC with a novel DNA topoisomerase I inhibitor, demonstrated superior bystander effect to overcome tumor heterogeneity [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 2878.