tbuckley/cabot-search huggingface dataset:
Abstract B075: Detection of early gastric carcinoma by micronuclei DNA from erythrocytes
Authors: Yuehua Han, Xingyun Yao, Haobo Sun, Cheng Fang, Peiwei Li, Honghao Liang, Jie Jin, Xiaofei Gao
Journal: Clinical Cancer Research (2024)

Abstract Background: Advancements in non-invasive diagnostic technologies for gastric carcinoma (GC), including serum microRNA and cell-free DNA assays, have shown promise but still face challenges in achieving consistent early detection. Micronuclei (MN), extranuclear bodies harboring fragmented chromosomal segments, are indicative of genomic instability and have been employed in genotoxicity assessments and cancer diagnostics. We have developed a novel technique (WO2021/228246 A1) for the purification and characterization of micronuclei DNA (MN-DNA) extracted from erythrocytes in peripheral blood. Here, we evaluated the potential of micronuclei DNA (MN-DNA) from 2ml peripheral blood for early gastric carcinoma detection and explored its application for early cancer diagnosis. Methods: We assembled a clinical cohort consisting of 425 healthy donors (HDs) and 282 gastric cancer patients, from whom 1-2 mL peripheral blood samples were collected. Participants were randomly allocated into training, validation, and independent test cohorts in a 7:2:1 ratio, ensuring similar distributions of cancer stages and gender. MN-DNA was isolated from erythrocytes and subjected to comprehensive whole-genome sequencing. Predictive machine learning models were constructed utilizing distinct tumor-associated MN-DNA features identified through genome-wide analysis to distinguish between HDs and GC. Results: Comprehensive genome-wide analysis of MN-DNA demonstrated pronounced disparities in distribution patterns between HDs and GC patients. The predictive model built on MN-DNA features achieved an AUC of 97.69% (95%CI: 95.57- 99.81%), with an 96.47% specificity and 91.07% sensitivity in the independent test cohort. The model identified early GC (stage 0-I) and advanced GC (stage II-IV) with sensitivities of 95.24% or 78.57%, respectively. Conclusions: Our results demonstrate that MN-DNA from 1-2mL peripheral blood enable accurate detection of GC, especially in early GC. As a type of cytoplasmic DNA, MN-DNA can provide a valuable tool for early cancer detection, offering different underlying mechanisms compared to current methods. Research sponsor: Timing Biotech. Citation Format: Yuehua Han, Xingyun Yao, Haobo Sun, Cheng Fang, Peiwei Li, Honghao Liang, Jie Jin, Xiaofei Gao. Detection of early gastric carcinoma by micronuclei DNA from erythrocytes [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B075.
Abstract B052: Plasma proteomic biomarkers reveal biological insights about the tumor microenvironment in melanoma patients after PD1 blockade
Authors: Samuel J. Wright, Izabella Zamora, Milan Parikh, Deepika Yeramosu, Lynn Bi, Sarah Kang, Marijana Rucevic, Moshe Sade-Feldman, Baolin Liu, Ngan Nguyen, Jamey Guess, Alexis Schneider, David Lieb, Elliot Woods, William Michaud, Aleigha R. Lawless, Tatyana Sharova, Gyulnara Kasumova, Michelle S. Kim, Ryan J. Park, Russell W. Jenkins, Samuel J. Klempner, Ryan J. Sullivan, Keith T. Flaherty, Nir Hacohen, Genevieve M. Boland, Arnav Mehta
Journal: Clinical Cancer Research (2024)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR018) of the Conference Program/Proceedings. Citation Format: Samuel J. Wright, Izabella Zamora, Milan Parikh, Deepika Yeramosu, Lynn Bi, Sarah Kang, Marijana Rucevic, Moshe Sade-Feldman, Baolin Liu, Ngan Nguyen, Jamey Guess, Alexis Schneider, David Lieb, Elliot Woods, William Michaud, Aleigha R. Lawless, Tatyana Sharova, Gyulnara Kasumova, Michelle S. Kim, Ryan J. Park, Russell W. Jenkins, Samuel J. Klempner, Ryan J. Sullivan, Keith T. Flaherty, Nir Hacohen, Genevieve M. Boland, Arnav Mehta. Plasma proteomic biomarkers reveal biological insights about the tumor microenvironment in melanoma patients after PD1 blockade [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B052.
Abstract B050: Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities
Authors: Christopher R Mueller, Keira Parr, Mihaela Mates, Andrew Robinson, Harriet Feilotter, Keira Frosst
Journal: Clinical Cancer Research (2024)

Abstract We have developed a version of our "methylation DETection of Circulating Tumour" DNA (mDETECT) assay that is able to sensitively and quantitatively monitor Non-Small Cell Lung Cancer (NSCLC). We used this assay to frequently assess the tumour burden of a small cohort (17 individuals) of patients undergoing first line monotherapy with pembrolizumab for metastatic disease. Patients were tested weekly or biweekly in the period immediately after initiation of treatment with radiological assessment being done at approximately 3 months. Radiologically non-responding patients showed constant or increased mDETECT levels over the 3 month time frame. Responding patients showed 2 different patterns, with some showing dramatically increasing mDETECT levels for a short period of time followed by a rapid decrease. Other responders showed an immediate decrease within the first few week of treatment. In both responder groups these decreases were associated with a longer term response. Continued monitoring did reveal eventual progression in some of these patients with increasing mDETECT levels being seen 4 to 6 months before radiological changes. In some non-responding patients complex responses were seen, with mDETECT levels varying significantly over time. In one non-responding patient the addition of carboplatin to their treatment regime did produce a temporary improvement in their mDETECT levels. Frequent assessment of tumour burden by a liquid biopsy such as mDETECT offers the opportunity to rapidly determine a patient's response to therapy and potentially modify treatments to improve responses. Citation Format: Christopher R Mueller, Keira Parr, Mihaela Mates, Andrew Robinson, Harriet Feilotter, Keira Frosst. Frequent monitoring of NSCLC immunotherapy using an mDETECT liquid biopsy reveals unexpected complexity and opportunities [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B050.
Abstract B072: Molecular targets of caffeine in breast cancer treatment: A network pharmacology approach
Authors: Kingsley A Osei, Justina S Owusu
Journal: Clinical Cancer Research (2024)

Abstract In Ghana, breast cancer leads in female cases (31.8%), demanding advanced treatments. Rising caffeine-filled energy drinks raise concerns. Yet, caffeine's role in breast cancer lacks understanding, urging more research. Our study uses network pharmacology and molecular docking to unravel the intricate molecular targets of caffeine in breast cancer, offering new therapies for this widespread disease We identified breast cancer-related targets from GEO datasets and TCGA databases, while caffeine targets were obtained from the SwissTarget Prediction database and literature. Common targets of both caffeine and breast cancer were considered using Venny software. PPI networks were generated using STRING and Cytoscape, identifying hub genes. Target proteins were annotated using the GO database, and pathway enrichment analysis was performed using KEGG. To investigate the binding affinity target proteins were retrieved from the Protein DataBank and docking studies were conducted using AutoDock Vina to explore the binding interactions between caffeine and potential target proteins identified. We identified 108 targets, and 6 common targets, including Cyclin-Dependent Kinase 1, Cyclin B1, Epidermal Growth Factor Receptor, Cyclin B2, Monoamine Oxidase A, and Carbonic Anhydrase 12 in relation to breast cancer. Gene Ontology (GO) and KEGG pathway enrichment analysis revealed their interactions in key pathways such as the P53 signaling pathway and Foxo signaling pathway, suggesting their critical roles in anti-breast cancer processes. Notably, caffeine exhibited the best overall binding affinity when interacting with CDK1, CCNB1, EGFR, and CCNB2 These findings provide valuable insights into the potential molecular targets and pathways associated with caffeine's anti-breast cancer effects, offering new strategies for therapeutic strategies. Citation Format: Kingsley A Osei, Justina S Owusu. Molecular targets of caffeine in breast cancer treatment: A network pharmacology approach [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B072.
Abstract A062: Insightful analysis: Harnessing aqueous humor ctDNA for retinoblastoma stratification
Authors: Sophia H Montigel, Tatsiana Ryl, Stefanie Volz, Elena Afanasyeva, Tatjana Wedig, Nathalie Schwarz, Stefan M Pfister, Kristian W Pajtler, Petra Ketteler, Kendra K Maaß
Journal: Clinical Cancer Research (2024)

Abstract Retinoblastoma (RB) the most common intraocular malignancy in children poses a significant challenge as traditional tissue biopsies are not feasible. Due to its critical location within the eye and the high risk of tumor seeding, clinicians are limited in performing molecular analysis-based risk stratification prior to enucleation. In this study, we explored the potential of aqueous humor (AH) as a source for minimally invasive liquid biopsies, aiming to establish a molecular profiling methodology for circulating tumor DNA (ctDNA) for risk stratification. We analyzed AH samples and corresponding tumor tissues from 19 enucleated eyes of patients diagnosed with RB. The extracted ctDNA from AH underwent low-coverage whole-genome sequencing (lcWGS) and methylation profiling. These data were then compared with the genomic and methylation landscapes of the matched tumor DNA. Additionally, we assessed the ability of AH- derived ctDNA to predict retinoblastoma methylation cluster. Our findings demonstrate a high concordance between ctDNA from AH and the primary tumor DNA in both methylation patterns and genomic alterations detected by lcWGS allowing the correct prediction of the retinoblastoma molecular group. The shared aberrations underscore the potential of AH as a reliable surrogate for tumor tissue in retinoblastoma. Additionally, the methylation profiles revealed consistent epigenetic modifications, further supporting the accuracy of AH-derived ctDNA in reflecting the tumor’s molecular characteristics. This study highlights the feasibility and effectiveness of using AH for molecular ctDNA genetic analysis in retinoblastoma. The overall high concordance between ctDNA profiles with primary tumor DNA and the ability to accurately predict RB methylation classes, highlights the superiority of the liquid biopsy approach overcoming the limitations of traditional biopsies and transforming the potential for early molecular analysis and risk stratification. This revolutionary technique could redefine pre-enucleation diagnostics, offering unprecedented insights and paving the way for tailored, precision medicine in retinoblastoma care. Citation Format: Sophia H Montigel, Tatsiana Ryl, Stefanie Volz, Elena Afanasyeva, Tatjana Wedig, Nathalie Schwarz, Stefan M Pfister, Kristian W Pajtler, Petra Ketteler, Kendra K Maaß. Insightful analysis: Harnessing aqueous humor ctDNA for retinoblastoma stratification [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A062.
Abstract A058: Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma
Authors: Hyung Keun Lee, So Young Kim, Soo-Hyun Chung, Sung Ill Jang, Bongkun Choi, Ji-Eun Kim, Dohee Yoon, Areum Yeo, Hyun Goo Kang, Jusung Lee, Yoon Ha Choi, Joon Seong Park, Yoolim Sung, Jong Kyoung Kim, Eun-Ju Chang, Dong Ki Lee
Journal: Clinical Cancer Research (2024)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a poor prognosis, largely due to late diagnosis and limited treatment options. The immunosuppressive tumor microenvironment (TME) further exacerbates the situation, hindering the effectiveness of traditional therapies. This study investigates the potential of IL-10R2/IL-22R1 expressing immune cells as novel biomarkers for early PDAC detection and recurrence monitoring, offering a potential avenue for improved patient outcomes. The research revealed a significant increase in the number of IL-10R2/IL-22R1 expressing immune cells in the peripheral blood of PDAC patients compared to healthy controls. These cells were found to infiltrate PDAC tissue and exhibit immunosuppressive functions, contributing to the TME's suppression of the immune response. Further investigation using a mouse model of PDAC demonstrated that early tumor progression was accompanied by a rise in IL-10R2/IL-22R1 expressing immune cells in the blood, highlighting their potential role in tumor development. In post-pancreatectomy patients, the study observed that elevated levels of IL-10R2+ immune cells were associated with earlier recurrence compared to the currently employed biomarker, CA19-9. This finding suggests that IL-10R2/IL-22R1 expressing immune cells could serve as valuable tools for predicting PDAC recurrence and potentially improving treatment outcomes. This research provides compelling evidence for the potential of IL-10R2/IL-22R1 expressing immune cells as promising biomarkers for early PDAC diagnosis and recurrence monitoring. However, further research is crucial to comprehensively understand their generation, function, and clinical utility. Larger-scale studies are needed to validate these findings and translate them into practical clinical applications for improved patient care. Citation Format: Hyung Keun Lee, So Young Kim, Soo-Hyun Chung, Sung Ill Jang, Bongkun Choi, Ji-Eun Kim, Dohee Yoon, Areum Yeo, Hyun Goo Kang, Jusung Lee, Yoon Ha Choi, Joon Seong Park, Yoolim Sung, Jong Kyoung Kim, Eun-Ju Chang, Dong Ki Lee. Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A058.
Abstract IA005: Tumor cell-based liquid biopsy to characterize prostate cancer
Authors: Daniel A Haber, Shyamala Maheswaran, Hongshan Guo, Joanna Vuille, Shih-Bo Huang, Ben S Wittner, Lecia V Sequist, Richard J Lee, Patricia AR Brunker, David T Miyamoto, Avanish Mishra, Mehmet Toner
Journal: Clinical Cancer Research (2024)

Abstract Circulating Tumor Cells (CTCs) hold the promise of comprehensive yet noninvasive molecular characterization of cancer cells during the course of tumor evolution and progression. To dissect the epigenetic profile of prostate CTCs, we undertook paired DNA methylation and RNA sequencing of single CTCs isolated from blood specimens of patients with prostate cancer. Across the genome, our study identified 40 core Partial Methylation Domains (PMDs) that arise early in tumorigenesis and are shared by all individual CTCs across multiple patients. Key among these is a single genomic locus harboring multiple interferon-inducible genes along with all the CD1 gene family members, implicated in innate immunity. Based on mouse models, we propose that early biallelic silencing of multiple genes residing within a single PMD may contribute to the escape from immune surveillance in prostate and potentially other cancers. Studies of CTC heterogeneity within individual patients are limited by the very small number of cells that can be isolated from standard 10ml blood volumes. To enable such analyses, we applied a new high throughput microfluidic platform, capable of processing an entire leukapheresis product, interrogating 2-3 L of blood volume equivalent. Applying this technology to patients with metastatic prostate cancer, we successfully enriched thousands of CTCs from individual cases, enabling the characterization of intra-patient heterogeneity at the level of cell morphology and marker expression, chromosome copy number variation and exome-wide genotyping, and transcriptionally-defined tumor cell subpopulations. Such high-volume microfluidic enrichment of CTCs constitutes a new dimension in liquid biopsies. Citation Format: Daniel A Haber, Shyamala Maheswaran, Hongshan Guo, Joanna Vuille, Shih-Bo Huang, Ben S Wittner, Lecia V Sequist, Richard J Lee, Patricia AR Brunker, David T Miyamoto, Avanish Mishra, Mehmet Toner. Tumor cell-based liquid biopsy to characterize prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr IA005.
Abstract A047: Detecting Hypoxic Circulating Tumor Cells (H-CTC) with a novel technique
Authors: Beatriz Zayas, Karoline Rios, Osvaldo Cox
Journal: Clinical Cancer Research (2024)

Abstract There is a continues need to develop technologies to detect and characterize circulating tumor cells that can become aggressive, metastatic, and hard to treat. Among these aggressive CTC are cells known as Hypoxic cell populations that learn to adapt and survive to low oxygen levels. Our project aims to test the applicability of a novel technique to detect Hypoxic Circulating Tumor Cells (H-CTC) that can move from tumors to circulating blood invading other tissues and becoming resistant to chemotherapy and radiation. The proposed assay incorporates a set of patented organic compounds as markers of hypoxic circulating tumor cells (H-CTC) with potential clinical applications. To date, our research has generated preliminary in-vitro studies with a novel NBQ-TOM demonstrating its capacity as markers of hypoxic human cancer cells in vitro. Comparison with the control Pimonidazole demonstrated the advantages of novel NBQ- TOM compounds as hypoxic marker. To determine the capacity of NBQ-TOM as hypoxic fluorescent marker, samples of 15 ml human whole blood were spiked with hypoxic or normoxic colon cancer cells (COLO 205). Spiked hypoxic or normoxic cells are then enriched, recovered, and treated with NBQ-TOM (25uM) for 24 hours. After treatment generated fluorescence is measured with an OPTIMA BMG Fluorimeter to demonstrate the significant formation of a fluorescent metabolite on hypoxic tumor cells in contrast to cells treated under normoxic environment. Also, fluorescence microscopy analysis confirmed the stronger fluorescence generation at hypoxic conditions. These preliminary results strongly support the applicability of these molecules for an in-vitro detection assay of hypoxic CTC in circulating blood that can become metastatic. Additional sensitivity and specificity analysis needs to be implemented. Citation Format: Beatriz Zayas, Karoline Rios, Osvaldo Cox. Detecting Hypoxic Circulating Tumor Cells (H-CTC) with a novel technique [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A047.
Abstract B070: Dissecting EV dynamics in the sequestration of doxorubicin from breast cancer cells
Authors: Sina Halvaei, Jing Xu, Suganthi Chittaranjan, Sharon Gorski, Karla Williams
Journal: Clinical Cancer Research (2024)

Abstract Background: Extracellular vesicles (EVs) are one of the three main analytes sought for in liquid biopsy development. EVs are released by all cell types including cancer cells and play a crucial role in cell-cell communication. Breast cancer cells have been shown to utilize EVs as a mechanism to sequester chemotherapeutic agents, thereby conferring resistance to treatment. This study investigates the role of EVs in doxorubicin (DOX) resistance in MDA-MB-231 breast cancer cells. Method: MDA-MB-231 cells were exposed to increasing dose of anthracycline for 6 and 12 months. Resistance was confirmed by cytotoxicity assay and western blot. Resistant and parent cells were labeled for immunohistochemistry and their EVs were isolated via ultracentrifugation. EVs were analysed using nanoscale flow cytometry and sent for mass spectrophotometry. Result: Using nanoscale flow cytometry, we optimized a method to detect DOX-carrying EVs based on the intrinsic fluorescence of the drug. We found that DOX-resistant cells exhibited lower intracellular DOX accumulation and higher expression of the EV marker CD63 compared to their parental counterparts. Conclusion: These results suggest that chemoresistant breast cancer cells may alter their EV production machinery to evade the lethal effects of DOX. Understanding this mechanism could lead to novel strategies to overcome chemoresistance in breast cancer. Citation Format: Sina Halvaei, Jing Xu, Suganthi Chittaranjan, Sharon Gorski, Karla Williams. Dissecting EV dynamics in the sequestration of doxorubicin from breast cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B070.