tbuckley/cabot-search huggingface dataset:
Abstract 4548: The association between tissue genomic alterations and ctDNA shedding in non small cell lung cancer
Authors: Robert Cameron, Anna Di Lello, Faith Abodunrin, Sulin Wu, Alessandra Esposito, Apameh Pezeshk, Valter Torri, Christine Bestvina, Marina Garassino
Journal: Cancer Research (2025)

Abstract Introduction: Tumor burden, stage and metastatic extent are associated with the presence of circulating tumor DNA (ctDNA). However, the association between genomic alterations and the presence of ctDNA remains unclear. Methods: We retrospectively analyzed patients with non-small cell lung cancer (NSCLC) with available Next-Generation Sequencing (NGS) analysis on both tissue and blood treated at the University of Chicago. NGS on tissue biopsies was conducted using the internal Oncoplus assay (168 genes). NGS on blood samples was conducted using the Guardant360 assay. Plasma ctDNA concentration was measured by the Variant Allele Frequency (VAF). Spearman rank correlation coefficient was used to assess the relationship between increasing number of mutations and VAF. Wilcoxon rank-sum test was used to compare the distribution of VAF between subgroups. Results: A total of 221 patients were identified. Adenocarcinoma was the predominant histological subtype, accounting for 89.6% (n=199) of cases. The cohort was predominantly Caucasian (55.4%) and female (66.2%). The median age at diagnosis was 65 years. At the time of index liquid biopsy, 85.1% of patients had metastatic disease. Among the 221 patients, 129 (58.6%) harbored actionable mutations, with EGFR exon 19 or 21 mutations being the most prevalent (n=80, 36.2%). This study found a weak but significant association between VAF and mutation count in the tissue biopsy: for total mutations including both significant alterations and variants of unknown significance (r = 0.146, p=0.032) and for significant mutations only (r = 0.160, p=0.018). These associations were stronger in the KRAS G12C mutated sub-cohort for both total (r=0.471, p=0.036) and significant mutations (r=0.573, p=0.008). Significantly higher ctDNA VAF was observed in TP53 (p=0.006) and STK11 (p=0.05) mutant tumors. Conclusions: Our results showed a correlation between increasing number of alterations and ctDNA shedding. The association was stronger for KRAS G12C mutated tumors. The relationship between genetic changes and ctDNA release is supported by the increased ctDNA VAF seen in TP53 and STK11 mutant tumors. Citation Format: Robert Cameron, Anna Di Lello, Faith Abodunrin, Sulin Wu, Alessandra Esposito, Apameh Pezeshk, Valter Torri, Christine Bestvina, Marina Garassino. The association between tissue genomic alterations and ctDNA shedding in non 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 4548.
Abstract 4325: FXYD5 plays diverse roles in immune evasion and tumor progression in prostate cancer
Authors: Ru Wen, G Edward W. Marti, Neeladrisingha Das, Zhengyuan Qiu, Nathan Lam, Eric E. Peterson, Zenghua Fan, Aram Lyu, Fernando Jose Garcia Marques, Abel Bermudez, Hongjuan Zhao, Lawrence Fong, Guillem Pratx, Donna M. Peehl, Sharon J. Pitteri, James D. Brooks
Journal: Cancer Research (2025)

Abstract FXYD5 is involved in various biological processes, including inflammation, tumor progression, drug resistance, and hypertension. It has been suggested as a potential biomarker for several cancers, with elevated levels found in ovarian and colon cancer. However, the role of FXYD5 in prostate cancer has not yet been elucidated. Here, we found that the FXYD5 was expressed in tumor cells by sc-RNA sequencing of human metastatic prostate tumor tissues. The expression levels of FXYD5 were higher in androgen receptor (AR)-negative prostate cancer cells compared to AR-positive prostate cancer cells. Intrinsically, FXYD5 knockout promoted PC3 cell proliferation, migration, and invasion. In vivo studies showed that FXYD5 knockout promoted PC3 tumor growth, while overexpression of FXYD5 inhibited PC3 tumor progression. However, in AR-positive 22Rv1 cells, overexpression of FXYD5 promoted tumor progression. In vitro assays indicate that overexpression of FXYD5 in PC3, C42B, and 22Rv1 cells reduces mitochondrial membrane potential and reactive oxygen species. Additionally, FXYD5 overexpression reduces lactate dehydrogenase activity and lactate levels in PC3 cells but has no effect on these parameters in 22Rv1 cells. In PC3 cells, FXYD5 overexpression promotes the formation of tight cell-cell interactions, accompanied by downregulation of membrane markers and nuclear enlargement. In contrast, these effects are not observed in 22Rv1 or C42B cells. Further, FXYD5 is identified as a potential Siglec-7 ligand by CRISPRi screen. FXYD5 knockout decreased Siglec-7 Fc binding capacity and enhanced the NK-cell mediated cytotoxicity in prostate cancer cells. In a humanized mouse model, 22Rv1 tumor growth was inhibited with human immune cell modulation. However, when FXYD5 was overexpressed in 22Rv1 cells, tumor growth was not impacted by immune cell-based therapy. This was due to the interaction of FXYD5 on cancer cells with Siglec-7 on immune cells, thereby inducing immunosuppressive signals. These findings suggest potential therapeutic strategies targeting FXYD5-based mechanisms. Citation Format: Ru Wen, G Edward W. Marti, Neeladrisingha Das, Zhengyuan Qiu, Nathan Lam, Eric E. Peterson, Zenghua Fan, Aram Lyu, Fernando Jose Garcia Marques, Abel Bermudez, Hongjuan Zhao, Lawrence Fong, Guillem Pratx, Donna M. Peehl, Sharon J. Pitteri, James D. Brooks. FXYD5 plays diverse roles in immune evasion and tumor progression 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 4325.
Abstract 5408: Unraveling c-MYC role in DNA replication origin licensing through non-canonical pathways
Authors: Dalia Fleifel, Eiman Elkoumy, Arthi Adavikolanu, Sidra Qayyum, Jeanette Cook
Journal: Cancer Research (2025)

Abstract Origin licensing is essential for DNA replication, confined to the G1 phase of the cell cycle, where human cells must license thousands of origins to ensure complete genome duplication. Insufficient licensing, or "underlicensing", leads to genome instability and increased sensitivity to chemotherapeutic agents. Altered G1 duration and dysregulated origin licensing are characteristic features of many cancers, potentially contributing to their aberrant cell proliferation. However, how origin licensing rates are controlled in cells with varying G1 lengths is poorly understood. Our research reveals that while cyclin E1 overproduction shortens G1 and causes severe underlicensing, c-MYC overproduction also shortens G1 but uniquely accelerates licensing, preventing underlicensing. *We identified a separation of function c-MYC mutant that fails to induce rapid licensing despite upregulating mRNA levels of licensing factors akin to wild-type c-MYC, indicating the involvement of non-canonical pathways beyond traditional transcriptional mechanisms*. c-MYC influence on global chromatin structure through hyperacetylation is pivotal. Our data show that c-MYC’s role in licensing acceleration depends on the recruitment of TRRAP—a transcription cofactor involved in chromatin modification—and the histone acetyltransferase GCN5. Notably, euchromatin is preferred for origin licensing in early G1. We hypothesize that heterochromatin may be rapidly licensed in c-MYC overproducing cells to compensate for potential underlicensing. We are currently profiling early versus late G1 cells overproducing c-MYC to determine the genomic locations of the licensed origins. Unraveling c-MYC downstream pathways regulating origin licensing could revolutionize therapeutic strategies by precisely controlling proliferation in MYC-driven cancers, increasing their sensitivity to DNA-damaging treatments, and paving the way for targeting non-canonical pathways in cancer therapy. Citation Format: Dalia Fleifel, Eiman Elkoumy, Arthi Adavikolanu, Sidra Qayyum, Jeanette Cook. Unraveling c-MYC role in DNA replication origin licensing through non-canonical 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 5408.
Abstract 4016: Understanding clinician level barriers and facilitators to managing cancer survivors with chronic conditions at community health centers
Authors: Maram Museitif, Bijal Balasubramanian, Gretchen H. Walton, Laura Aubree Shay, Hilary Ma, Simon Lee
Journal: Cancer Research (2025)

Abstract Background: Primary care clinicians (PCCs) play a critical role in delivering comprehensive care to patients with chronic conditions, including cancer survivors. Community health centers (CHCs) serve as primary healthcare facilities, providing accessible and affordable care to underserved and vulnerable populations, including cancer survivors. Despite the essential role of CHCs, significant gaps remain in knowledge and research training regarding survivorship care within these settings. Given the rising population of cancer survivors in the United States, addressing these gaps is crucial to ensuring high-quality survivorship care. This study aimed to assess the barriers and facilitators PCCs encounter when providing survivorship care to cancer survivors with chronic conditions at CHCs. Methods: Qualitative in-depth interviews were conducted with PCCs from two healthcare systems, encompassing four urban CHCs in Texas during two phases. The research team developed semi-structured interview guides to explore barriers and facilitators in survivorship care. Interviews were conducted via phone or WebEX, a virtual platform, and were audio-recorded and transcribed verbatim by a certified transcription service. A team member reviewed the transcripts to ensure accuracy. Data were analyzed using an adapted immersion and crystallization approach, guided by the Chronic Care Model (CCM), to identify key themes related to survivorship care. Results: Ten PCCs participated in the study. Qualitative analysis identified five key barriers to delivering high-quality survivorship care: (1) role ambiguity between PCCs and specialists, (2) inaccessibility of survivorship clinical guidelines, (3) limited communication between PCCs and oncologists, (4) inconsistent documentation of medical history, and (5) patient socioeconomic challenges, including financial difficulties. Pragmatic solutions were proposed to mitigate these barriers, and a patient-centered approach emerged as a key facilitator in improving care delivery. Conclusions: These findings highlight valuable opportunities to enhance survivorship care within CHCs by addressing identified barriers and leveraging facilitators to foster patient-centered, high-quality care for underserved cancer survivors. The utilization of the CCM framework provided deeper insights into the specific gaps and challenges PCCs face in CHCs. Citation Format: Maram Museitif, Bijal Balasubramanian, Gretchen H. Walton, Laura Aubree Shay, Hilary Ma, Simon Lee. Understanding clinician level barriers and facilitators to managing cancer survivors with chronic conditions at community health centers [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 4016.
Abstract 3535: Targeting cervical cancer: VC-2 as a vaccine and treatment for HPV infections
Authors: Mohammed T. Hussain, Robert Ellis, Kiran Fida, Mariano Carossino, Brent A. Stanfield
Journal: Cancer Research (2025)

Abstract Cervical cancer is a major cause of mortality worldwide and has been attributed to long-lasting (persistent) infections with the human papillomavirus (HPV). Although more than 50 types of HPVs are known the infect the genital tract, fewer than a dozen of them are regularly linked to cervical cancers leading to these types being designated as “high risk” HPVs. The infectious nature of HPVs procures the need for preventative vaccines against cervical cancer, and current vaccines such as Gardasil-9 and Ceravix achieve high efficacy in protection. However, once infections are established, preventative vaccines are inefficient in treating the malignancies. In HPV-associated tumors, the E7 oncoprotein is an ideal target for immunotherapeutic strategies and has been shown to be a likely target to treat cervical cancer. HSV, particularly HSV-2, often coexists with HPV due to similar transmission routes. Studies suggest that HSV infections may enhance the oncogenic effects of HPV by increasing inflammation, immune system modulation, and promoting a more favorable environment for HPV persistence and progression to cancer. Engineered Herpes Simplex Virus Type-1 (HSV-1) has been a promising candidate in treating established cancers and has been shown to be efficacious in improving anti-tumors responses and controlling tumor metastasis. Therefore, in this study, we aim to utilize the engineered HSV-1 strain (VC-2) to treat established cervical cancers and evaluate its efficacy as a prophylactic vaccine. The mice inoculated with the Tal-3 cervical cancer cell line show metastasis in the lungs and formation of large tumors. Moving forward, we would like to conduct therapeutic and prophylactic studies evaluating the reengineered VC-2 towards treating cervical cancer. Citation Format: Mohammed T. Hussain, Robert Ellis, Kiran Fida, Mariano Carossino, Brent A. Stanfield. Targeting cervical cancer: VC-2 as a vaccine and treatment for HPV infections [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 3535.
Abstract 3858: Therapeutic targeting of cofilin-1 phosphorylation by peptidomimetics inhibits lung cancer metastasis
Authors: Min-Ying Lin, Jyh-Der Leu, Chun-Yi Wu, Yi-Jang Lee
Journal: Cancer Research (2025)

Abstract Background: The main challenges in the clinical management of lung cancer are distant metastasis and recurrence. Targeting the destabilization of actin dynamics has become a critical approach to slowing the rapid proliferation of tumor cells. However, a specific class of anti-metastatic drugs is still being uncovered. Methods: The analysis of gene expression of ADF/cofilin family by public database in clinically relevant. Combination of the endogenous protein level of CFL-1, its phosphorylation status, and cellular invasion activity in various lung cancer cell lines. We used synthetic peptide to interfere LIMK/CFL-1 regulatory pathway to produced anti-metastatic and survival benefits in a xenograft lung cancer model. Furthermore, the biological characteristics of peptide labeled with metal radionuclide both in vitro and in vivo were also be evaluated. Results: Over-expression of cofilin-1 (CFL-1) gene was associated with the incidence and survival rate of lung adenocarcinoma using the in-silico analysis. CFL-1 proteins were also differentially elevated in various NSCLC cell lines. Notably, we found that the phosphorylation level of CFL-1 at serine 3 (Ser3), rather than the total CFL-1, was better correlated with the invasion potential of NSCLC cells. Here, we developed synthetic CFL-1 mimetic peptides (CMP) to inhibit endogenous CFL-1 phosphorylation and evaluated their effects using highly metastatic NSCLC cells. The SPECT/CT imaging demonstrated that CMP labeled with 99mTc can be detected in an orthotopic lung tumor. Furthermore, CMP can act as a competitive decoy of cofilin kinase, demonstrating anti-metastatic effects and prolonged survival in a xenograft model, with no significant toxicity observed. Conclusion: This study demonstrates that the phosphorylation level of CFL-1 at serine 3 is strongly correlated with the metastatic potential of lung cancer, and interfering with its phosphorylation could be a promising strategy for lung cancer treatment. Citation Format: Min-Ying Lin, Jyh-Der Leu, Chun-Yi Wu, Yi-Jang Lee. Therapeutic targeting of cofilin-1 phosphorylation by peptidomimetics inhibits lung cancer metastasis [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 3858.
Abstract 5473: Development of a novel fluorescent ELISpot assay using the CeligoTMImage Cytometer
Authors: Wen-Chieh Liao, Julia Abdalla, Carolina Franco Nitta, Mackenzie Pierce, Bo Lin, Jessie Ni
Journal: Cancer Research (2025)

ELISpot and its variant, fluorescent ELISpot (FluoroSpot), are commonly used methodologies that monitor and detect cytokine and/or antibody secretion from peripheral blood mononuclear cells (PBMCs). Conventional ELISpot and FluoroSpot assays utilize PVDF-membrane plates, which require labor-intensive washing steps that may introduce variability in performance and results. Here, we have developed a novel FluoroSpot assay using polystyrene-, clear-bottom microplates with simplified automated washing steps to minimize operator variability and error. In this work, we assessed multiple critical cellular immune-related activities, including IL-6, IFN-g, and TNF-a secretion in PBMCs using this novel FluoroSpot methodology in comparison to the conventional ELISpot assay. To detect cytokine secretion of IL-6, IFN-g, and TNF-a, the Celigo™ Image Cytometer (Revvity Health Sciences, Inc., Lawrence, MA) was incorporated to capture whole-well images of fluorescently labeled detection antibodies. Results for both methodologies were comparable to one another, validating the use of polystyrene plates on Celigo™ as opposed to PVDF-membrane plates. In addition to FluoroSpot detection, the Celigo™ was used as a quality control check to provide a comprehensive analysis of live cell distribution prior to performing the FluoroSpot assay. Live cell imaging results were used to correlate downstream cytokine-releasing cell spot formation results. Combinational use of the novel FluoroSpot polystyrene plate with the Celigo™ reduced operator variability and errors, while streamlining a multiparametric analysis to identify the number of fluorescent spots, spot morphology (size), and whole-well mean fluorescence intensity values. This methodology may prove useful for researchers interested in monitoring and detecting cytokine and/or antibody-releasing PBMCs. Citation Format: Wen-Chieh Liao, Julia Abdalla, Carolina Franco Nitta, Mackenzie Pierce, Bo Lin, Jessie Ni. Development of a novel fluorescent ELISpot assay using the CeligoTMImage Cytometer [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 5473.
Abstract 2457: Prognostic value of CD8+ T-cells at the invasive margin is comparable to immune score in non-metastatic colorectal cancer: A prospective multicentric cohort study
Authors: Durgesh Wankhede, Niels Halama, Matthias Kloor, Dominic Edelmann, Hermann Brenner, Michael Hoffmeister
Journal: Cancer Research (2025)

Abstract Background: Immunoscore predicts colorectal cancer prognosis but faces adoption barriers due to complex software and reimbursement issues. This study used open-source methods to explore a simplified prognostic model in non-metastatic CRC by focusing on single T-cell markers. Methods: A multicentric prospective cohort study in non-metastatic CRC patients assessed CD3+ and CD8+ tumor infiltrating lymphocytes (TILs) in the invasive margin (IM) and tumor core (TC) using QuPath. An immune cell score, based on TIL densities (CD3-IM, CD8-IM, CD3-TC, CD8-TC), was calculated similarly to the Immunoscore®. A split sample approach (70:30) estimated adjusted hazard ratios for cancer-specific survival (CSS) in training and validation sets. CART analysis identified the most prognostic TIL, and its model was compared to an immune cell score model for performance (Brier score) and discrimination (Concordance Probability Estimate, CPE). Results: Over a median follow-up of 9.0 years, 203 CRC-specific deaths occurred among 1, 260 patients. CART-selected CD8-IM was the most prognostic TIL at a cut-off of 231 cells/mm2. Patients with CD8-IMHi had better CSS than CD8-IMLow in both training (HR 0.58, 95% CI 0.40-0.84) and validation sets (HR 0.35, 95% CI 0.21-0.60). Brier scores of CD-8IM and immune cell score survival models were comparable in both training and validation cohort, whereas the survival discrimination of CD8-IM slightly outperformed the immune cell score in the validation set (CPE: CD8-IM 0.748, IS 0.730). Conclusion: CD8-IM alone provided prognostic information comparable to the immune cell score. Simplified, cost-effective TIL assessments could improve clinical translation and guide adjuvant therapy in early-stage CRC. Citation Format: Durgesh Wankhede, Niels Halama, Matthias Kloor, Dominic Edelmann, Hermann Brenner, Michael Hoffmeister. Prognostic value of CD8+ T-cells at the invasive margin is comparable to immune score in non-metastatic colorectal cancer: A prospective multicentric cohort study [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 2457.