tbuckley/cabot-search huggingface dataset:
Abstract 2788: Targeting miR-92b reduces neurosphere formation in glioblastoma cancer stem cells
Authors: Annelis O. Sánchez-Álvarez, Diego García-Ortiz, Misael Rivera-García, Alanis M. Labeaga-Sainz, Pablo E. Vivas-Mejia
Journal: Cancer Research (2025)

Abstract Glioblastoma (GBM) is a grade IV brain tumor with a dismal prognosis, driven by aggressive brain tumor-initiating cells (BTICs). This study focuses on targeting microRNA-92b-3p (miR-92b-3p), a microRNA aberrantly overexpressed in GBM that correlates with poor patient outcomes. We utilized primary BTIC neurospheres M1123 and GBM1A, derived from GBM patients, to investigate miR-92b-3p's role in tumor progression and therapeutic resistance. Our findings revealed a striking 40-fold higher basal expression of miR-92b-3p in GBM1A compared to M1123. Functional studies showed that miR-92b-3p inhibition significantly disrupted neurosphere formation in both cell lines up to 96 hours post-transfection, highlighting its essential role in maintaining GBM stemness. Additionally, the IC50 values for temozolomide, the standard GBM chemotherapeutic agent, were 27 µM for M1123 and 30 µM for GBM1A, suggesting similar baseline resistance. Ongoing experiments are exploring whether miR-92b-3p inhibition sensitizes BTICs to temozolomide, potentially enhancing its efficacy. These results underscore miR-92b-3p’s critical role in neurosphere maintenance and chemoresistance in GBM cancer stem cells. Its overexpression may serve as a biomarker for aggressive tumor behavior, and its inhibition represents a promising therapeutic strategy to target BTICs, disrupt GBM progression, and improve patient outcomes. Citation Format: Annelis O. Sánchez-Álvarez, Diego García-Ortiz, Misael Rivera-García, Alanis M. Labeaga-Sainz, Pablo E. Vivas-Mejia. Targeting miR-92b reduces neurosphere formation in glioblastoma cancer stem 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 2788.
Abstract 3214: The duration of immune checkpoint inhibitors (ICI) in oncology: Longer is not better
Authors: Farah Mazahvreh, Samuel L. Schach, Liyan Mazahreh, A. Mazin Safar
Journal: Cancer Research (2025)

Abstract ICI addition to the oncology armamentarium provided significant therapeutic benefits. Standard schedule of ICI calls for 2-year regimen without rational justification. Doses selected clearly do not adhere to classic maximal tolerated dose since ICIs were doubled at longer dose intervals. Theoretically however, multiple concerns can be proposed to question the 2-year duration. In human neoadjuvant melanoma studies examining ICI effect on effector T-cells comprehensively documented the expected clonal expansion in target cells but this was noted only for few weeks and did not continue upon repeated dosing, a major challenge to the current standard dosing schedule. Therapeutic T-cell transfers administer a single dose of 109 , a bulk that is expected to require 2-3 weeks of lymphocyte proliferation. Neutralizing antibodies have been reported in multiple studies, but notably without detriment to the therapeutic impact. Lastly, published and unpublished cases confirm lasting benefits (in years) after single ICI dosing. We hypothesized that benefits of ICI depend mostly, if not entirely, on the first, or few initial doses; that doses later in time can be delivered but add little if anything to the therapeutic impact. Methods/Results: we reviewed published ICI monotherapy or chemo-ICI which provided individual swimmers’ plot in stage 4 melanoma, renal cell and NSCLC. We extracted the median survival (MS) of those who received variable ICI durations excluding progression as the cause for halting therapy. Patients with progressive disease beyond 6 months, were included because they received considerable durations of ICI and might enjoy lasting benefits. We report the MS in the times depicted in the table. Our data reveal comparable results in all subgroups supporting our hypothesis. Conclusions: Despite standard recommendations, there is considerable rationale in addition to our current data to challenge the common duration of ICI and substantiate a far more limited exposure to ICI. Table ICI Duration Median Survival (Months) Number of Cases 1-3 months 27 29 3-6 months 31.5 24 6-12 months 32 63 12-18 months 35 30 18-24 months 37 47 24+ months 48 32 Citation Format: Farah Mazahreh, Samuel L. Schach, Liyan Mazahreh, A. Mazin Safar. The duration of immune checkpoint inhibitors (ICI) in oncology: Longer is not better [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 3214.
Abstract 678: A 10-second lipidomic based approach to diagnose common spinal tumor types with picosecond infrared laser mass spectrometry
Authors: Alexa Fiorante, Michael Woolman, David Munoz, Taira Kiyota, Lan Anna Ye, Yasamine Farahmand, Darah Vlaminck, Francis Talbot, Sunit Das, Gelareh Zadeh, Howard Ginsberg, Ahmed Aman, Arash Zarrine-Afsar
Journal: Cancer Research (2025)

Abstract Intradural extramedullary spinal neoplasms account for ∼40% of all diagnosed spinal tumors. Of that, meningioma and schwannoma are the most common. However, improving the surgical outcomes for these spinal neoplasms requires precise intraoperative diagnosis provided by highly trained neuropathologists. Through a retrospective study of n=257 patient specimens, we demonstrate that 10-second picosecond infrared laser mass spectrometry (PIRL-MS) can robustly and objectively diagnose commonly occurring spinal tumor types with the sensitivity and specificity values of (93±1)% and (97±2)%, respectively. This classification utilizes n=41 cellular lipids including phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, and ceramides, whose identities were established using high-resolution tandem mass spectrometry. The identified lipids form a ‘molecular array’ for robust diagnosis of meningioma and schwannoma tumors by non-pathologists in a manner like genomic, transcriptomic, or methylomic arrays used to diagnose brain cancer types, albeit on a faster timescale of seconds as opposed to hours. Furthermore, when subjected to the presence of additional intradural extramedullary spinal tumor types in the differential diagnosis, the generalizability and robustness of the identified molecular array rendered correct classification even in the presence of data not seen previously by the model. PIRL-MS mediated pathology stratifies the resection risk such that complete removal of certain spinal neoplasms such as meningioma tumors with dural excision could be justified to improve the surgical outcomes. Thus, providing informed surgical care even in the absence of intraoperative consults, addressing the human resource limitations in settings that are understaffed in neuropathology. Here, the current state of PIRL-MS device development allows operation by anyone with basic laboratory skills. Citation Format: Alexa Fiorante, Michael Woolman, David Munoz, Taira Kiyota, Lan Anna Ye, Yasamine Farahmand, Darah Vlaminck, Francis Talbot, Sunit Das, Gelareh Zadeh, Howard Ginsberg, Ahmed Aman, Arash Zarrine-Afsar. A 10-second lipidomic based approach to diagnose common spinal tumor types with picosecond infrared laser mass spectrometry [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 678.
Abstract 3717: A digital patient &amp; simulated clinical trial of cytarabine treatment
Authors: Gilad Silberberg, Stefano Cairo, Mara Gilardi, Brandon Walling, Marianna Zipeto, Michael Ritchie
Journal: Cancer Research (2025)

Abstract Historically, computational models have primarily relied on single-omic datasets, particularly transcriptomic data, to predict cancer sensitivity to drugs. These models often identified single gene alterations as biomarkers of drug response. While informative, the predictive potential of these biomarker panels remains limited. Moreover, these same panels have failed to predict potential toxicities associated with anti-cancer drugs. This underscores the urgent need to construct more robust biomarker panels capable of not only predicting patient response but also anticipating potential toxic effects. To address the complexity of cancer biology, we leveraged Champions’ extensively annotated bank of over 1500 Patient-Derived Xenograft Models (PDX). to create the deepest multi-omic dataset, incorporating proteomics, transcriptomics, genomics, and phenotypic data. Simultaneously, we assembled a comprehensive multi-omic normal tissue dataset, encompassing samples from major organs. In this work, we present an integrated approach to construct a digital patient capable of predicting both sensitivity and toxicity concerns by leveraging this rich multi-omics dataset. Our strategy involved pharmaco-pheno multi-omics integrations. Specifically, we conducted an ex-vivo cytotoxicity assay to establish sensitivity and resistance status to cytarabine using a panel of primary Acute Myeloid Leukemia (AML) samples. These samples had been previously characterized through proteomics, transcriptomics, and immunophenotypic analyses. The resulting cytotoxicity data, along with all omics and phenotypic information, were input into an N-based machine learning platform that leveraged partial least square Differential analysis. The output yielded a panel of multi-omics biomarkers predictive of cytarabine response. When prospectively applied to a new set of AML samples, our biomarker panel successfully predicted sensitivity in all but one sample. Intriguingly, the model achieved a 57% objective response rate. Furthermore, when we extended the model to normal tissue data, data suggested potential toxicity concerns for bone marrow, lung, heart, and peripheral nervous system. These findings correlate with observations in the clinic, therefore highlighting the potential use of digital patient strategies to simulate clinical trials. Citation Format: Gilad Silberberg, Stefano Cairo, Mara Gilardi, Brandon Walling, Marianna Zipeto, Michael Ritchie. A digital patient &amp; simulated clinical trial of cytarabine treatment [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 3717.
Abstract 3716: Discovery of macrocyclic peptides TTA-121 as insulin receptor modulators with anticancer potential: An integrated <i>in-silico</i> and <i>in-vitro</i> investigation
Authors: Veera Chandra Sekhar Reddy Chittepu, Poonam Kalhotra, Tzayhri Osorio-Gallardo, Tzayhri Gallardo-Velazquez, Guillermo Osorio-Revilla
Journal: Cancer Research (2025)

Abstract Insulin receptor (INSR), and Insulin-like growth factor (IGF-1R) are significantly similar to each other, and upon activation by ligands increases cell proliferation, differentiation and metastasis. In addition, for the cancer cells to acquire resistance to existing FDA approved one or downstream of it signaling pathways. So, identification of peptides to participate in the INSR/IGF-1R signaling pathway and possess anticancer is one of the upcoming strategies to treat cancer, and diabetes. In this study, we applied bioinformatics tools to analyze structure-activity relationships (SAR) of chemicals or peptides as insulin receptor (INSR) modulators to identify and gain the molecular insights into structural features responsible for INSR modulators. Later, commercially available cyclic peptide libraries are screened to possess the INSR modulator features, followed by molecular docking simulations/molecular dynamics revealed the binding mode, flexibility, and interacting residues of cyclic peptides which were similar to the binding of insulin-to-insulin receptor. To further validate our in-silico predictions, we conducted an intrinsic fluorescence assay, that demonstrated peptides like TTA-121 changed emission levels like insulin, mimicking insulin function or participating in insulin signaling pathway. Further, we carried out cancer cell proliferation assays in different cancer models like breast, lung and prostate cancer models to validate the potential of chosen peptides as anticancer agents. Our findings establish TTA-121 as a promising anticancer agent. On going studies are aimed to understand further TTA-121, its derivatives and in combination with standard drugs in clinical care are synergistic or additive and elucidating the mechanism of action. Overall, this study highlights the potential of cyclic peptides and its derivatives as INSR modulators and supports their use as standalone treatments or in combination with existing anticancer drugs would ultimately help in development of new cancer therapeutics to benefit cancer care. Citation Format: Veera Chandra Sekhar Reddy Chittepu, Poonam Kalhotra, Tzayhri Osorio-Gallardo, Tzayhri Gallardo-Velazquez, Guillermo Osorio-Revilla. Discovery of macrocyclic peptides TTA-121 as insulin receptor modulators with anticancer potential: An integrated in-silico and in-vitro investigation [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 3716.
Abstract 2303: The impact of adherence to cancer prevention guidelines on cancer risk, cancer incidence and mortality in a large cohort of Canadian adults
Authors: Samuel S. Fiati-Kenston, Rachel A. Murphy, Jerry M. Spiegel, Trevor J. Dummer
Journal: Cancer Research (2025)

Abstract Background: The World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR) publish behavioral guidelines for cancer prevention. The guidelines provide standards on body weight, physical activity, diet, alcohol consumption, and smoking. This study examined the impact of adherence to these guidelines on cancer incidence and mortality in a large cohort of Canadian adults. Methods: Data were obtained from the British Columbia Generations Project (BCGP), a longitudinal cohort of 30, 000 adults aged 35-69 years recruited between 2009 and 2015, with a median follow-up of 10 years. Participants with a baseline cancer diagnosis were excluded, leaving 23, 482 eligible individuals. A 3-level adherence score was constructed for each guideline. Cox proportional hazard models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer incidence and mortality, adjusting for sociodemographic and health covariates. Propensity score matching was conducted to assess the robustness of the results. Results: 3, 068 new cancer cases and 769 cancer deaths were recorded during follow-up. Full adherence to the WCRF/AICR guidelines was achieved by only 19% of men and 31% of women. High adherence was associated with a significant reduction in all cancer incidence, with HRs of 0.81 (95% CI: 0.68-0.92) for women and 0.82 (95% CI: 0.73-0.95) for men. Cancer mortality was also lower among adherent individuals, with HRs of 0.83 (95% CI: 0.66-1.09) for women and 0.86 (95% CI: 0.70-0.96) for men. Additionally, total mortality decreased by 14% in women (HR = 0.86; 95% CI: 0.69-0.95) and 11% in men (HR = 0.89; 95% CI: 0.72-0.93). These associations remained robust after adjusting for sociodemographic and health covariates and were confirmed through propensity score matching. Conclusions: Adherence to cancer prevention guidelines was associated with lower cancer incidence and mortality in both men and women. These findings highlight the importance of lifestyle modifications to reduce cancer risk among Canadian adults. Citation Format: Samuel S. Fiati-Kenston, Rachel A. Murphy, Jerry M. Spiegel, Trevor J. Dummer. The impact of adherence to cancer prevention guidelines on cancer risk, cancer incidence and mortality in a large cohort of Canadian adults [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 2303.
Abstract 2329: Understanding epigenetic-driven transposable re-expression and its impact on immune activation in the serrated pathway of colorectal tumorigenesis
Authors: Zhengyi Chen, Sojung Lee, Alan J. Simmons, Robert J. Coffey, Martha J. Shrubsole, Jason W. Wong, Ken S. Lau
Journal: Cancer Research (2025)

Abstract An active immune system plays a central role in preventing the progression from precancerous lesions to invasive cancers. Identifying the molecular markers that dictate effective immune surveillance is essential for advancing cancer prevention strategies. A higher level of immune cell infiltration is observed in serrated lesions, a subtype of colorectal premalignant lesions, in comparison to the other common subtype, conventional adenoma. However, the mechanism underlying the elevated immune response in serrated lesions remains poorly understood because hypermutation, which is considered as the source of immunogenicity conventionally, is absent in serrated lesions. One alternative source of immunogenicity can be transposable elements (TEs), which are mobile DNA sequences typically epigenetically silenced in mature tissues but expressed in fetal developmental stage and cancers. We hypothesize that aberrant expression of TEs drives immune activation in serrated lesions. Notably, only serrated lesions exhibit a fetal gene expression program, suggesting a potential link to epigenetically deregulated TE expression mediated by the PIWI-piRNA pathway. We quantify and compare TE expression and methylation levels across subtypes of colorectal precancers and normal tissues, integrating these data with spatial transcriptomics to elucidate the relationship between TE expression and immune cell distribution. Our results reveal a significantly higher number of differentially expressed TEs in serrated lesions compared to conventional adenomas and suggest a positive association between TE expression and the immunogenic landscape in serrated lesions. These findings inform strategies to reprogram colorectal precancers toward an anti-tumor immune environment, offering potential benefits for cancer prevention and early immuno-intervention strategies in colorectal cancer. Citation Format: Zhengyi Chen, Sojung Lee, Alan J. Simmons, Robert J. Coffey, Martha J. Shrubsole, Jason W. Wong, Ken S. Lau. Understanding epigenetic-driven transposable re-expression and its impact on immune activation in the serrated pathway of colorectal tumorigenesis [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 2329.
Abstract 1832: Identifying GSK3b inhibitor as a radiation induced type I interferon stimulator in lung cancer
Authors: Chen Braun, Nan Li, Steven H. Lin
Journal: Cancer Research (2025)

Radiation therapy (RT) is commonly used to treat multiple tumor types to reduce the risk of tumor recurrence. Despite impressive clinical responses only a subset of patients responds to RT, due to the lack of an adequate immune response within lung tumors. There is a strong motivation to develop novel approaches to overcome immunosuppression in tumors after radiation therapy. Here, we aim to identify pathways that could specifically augment type I interferon (IFN) response with RT to bypass the immune suppressive effects. We combined radiation and &amp;gt;700 pharmacological inhibitors in a high throughput screen to identify agents that induced type I IFN response. We revealed a GSK3β inhibitor (GSK3βi), Kenpaullone, as a drug hit that induced synergistic response with RT to enhance type I IFN expression. The selected GSK3βi was validated for its IFNβ1 induction in the mRNA and protein levels in multiple lung cancer cell lines, and by examining the associated AKT/GSK3β/IRF3 pathway. The effectiveness of this unique GSK3βi-RT combination to enhance IFNβ1 immunologic stimulation was tested in syngeneic tumor bearing animals and significantly reduced tumors size compared to radiation or drug alone. COMET analysis from mice tumors showed that combination therapy increased T cells and M1 macrophages at the tumor microenvironment (TME), while M2 macrophages and PDL-1 decreased. This pharmacological-RT combination approach has the potential to enhance the immunologic response to RT in lung cancer patients to reduce tumor burden in those that already exhausted standard of care therapies. Citation Format: Chen Braun, Nan Li, Steven H. Lin. Identifying GSK3b inhibitor as a radiation induced type I interferon stimulator in 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 1832.