tbuckley/cabot-search huggingface dataset:
Abstract 6687: Micromanaging resistance: microRNA expression and chemoresistance in testicular germ cell tumors
Authors: Ratnakar Singh, Kelly Kries, Aayush Gupta, Amy Li, Zeeshan Fazal, Doha Shokry, Raya Boyd, Brayden Rennels, Sarah J. Freemantle, Michael J. Spinella
Journal: Cancer Research (2025)

Abstract Testicular germ cell tumors (TGCTs) are the most common type of cancer among young men, and incidence has increased over the past 40 years. Approximately 80% of patients with metastatic TGCTs can be cured with chemotherapy; however, those patients that develop resistance to treatment often have a poor prognosis. Despite efforts to identify clear genetic factors that determine chemotherapy sensitivity and resistance in TGCTs, recent research has shifted focus toward the role of epigenetics in maintaining sensitivity to drugs like cisplatin and decitabine. Epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs (miRNAs), play a crucial role in regulating gene expression. Prior studies in somatic cancers have linked differential expressions of miRNAs to drug resistance. In this study, we hypothesized that the response of TGCTs to cisplatin and decitabine is partially influenced by miRNA expression. Through miRNA sequencing analysis followed by RT-qPCR validation, we identified distinct patterns of miRNA expression that correlate with resistance to cisplatin and decitabine in TGCTs. Consistent with our previous findings on protein coding gene expression, we observed that 54 miRNAs were reciprocally expressed between cells resistant to decitabine and those resistant to cisplatin. In follow-up analysis, we selected a subset of these reciprocally regulated miRNAs and predicted their target genes using miRDB and TargetScan. Downstream miRNA-RNA interactive analysis, enrichment analysis, and validation assays are ongoing and will be presented. Together, our study aims to elucidate the mechanistic roles of miRNAs in chemosensitivity and chemoresistance in TGCTs. The findings from this study will also support precise diagnosis and personalized treatment strategies for patients with TGCTs. Citation Format: Ratnakar Singh, Kelly Kries, Aayush Gupta, Amy Li, Zeeshan Fazal, Doha Shokry, Raya Boyd, Brayden Rennels, Sarah J. Freemantle, Michael J. Spinella. Micromanaging resistance: microRNA expression and chemoresistance in testicular germ cell tumors [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 6687.
Abstract 467: Programmable transcription factors as protein adjuvants for cancer immunotherapy
Authors: Nicholas Truex
Journal: Cancer Research (2025)

Abstract Immunotherapies are transforming clinical oncology by exploiting immune pathways to improve cancer treatment outcomes and provide long-term remission. Anticancer immune pathways are typically activated with dose regimens of antibodies, engineered cytokines, salt or oil emulsions, oligonucleotides, or lipid nanoparticles, which ultimately induce transcription and translation of interferon-stimulated genes that instruct the immune system to respond to tumors. These and other molecular adjuvants are widely used to stimulate broad inflammatory signals but are also associated with abnormal cytokine expression levels and tissue toxicity. To address the challenge of nonspecific activation and to improve antitumor immunity, our group is developing artificial transcription factor (ATF) proteins as a generalizable technology platform to target and control specific immune signaling pathways. This presentation will describe the design and characterization of these ATF proteins, including biophysical, biological, and antitumor properties, and demonstrate their therapeutic potential as gene- and protein-based adjuvants for cancer immunotherapy. Citation Format: Nicholas Truex. Programmable transcription factors as protein adjuvants for cancer immunotherapy [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 467.
Abstract 7345: Differences in complete screening adherence across age, income, and education groups
Authors: Kierstin M. Faw, Jamal R. Winn, Robert A. Smith, Ahmedin Jemal, Parichoy Pal Choudhury, Priti Bandi, Jordan A. Baeker Bispo, Alpa V. Patel
Journal: Cancer Research (2025)

Abstract There is limited knowledge of the sociodemographic characteristics of individuals who are fully adherent to all recommended cancer screening tests. Understanding these cancer screening gaps may provide insights into subpopulations who may benefit from interventions to increase overall early cancer detection. The Cancer Prevention Study- 3 is a prospective cohort study established by the American Cancer Society (enrollment 2006-2013). Between enrollment and 2018, cancer-free participants reported cancer screening tests (mammography, colonoscopy, sigmoidoscopy, stool testing, and low dose lung computed tomography (CT) scans) and year(s) of each screening. Eligibility for each test was determined using 2018 American Cancer Society guidelines. For each person, an adherence score was calculated based on the number of eligible screenings and whether they were adherent. Patterns of adherence were compared across age, education, and income groups using an ANOVA to determine statistical significance. 129, 927 individuals were included in this analysis. Men had a higher proportion of no screening adherence (17%), and complete adherence (81%) compared to women, 8% and 67%, respectively. For those 45-55 years old (N=37, 393), approximately 46% were not completely adherent, compared to only 24% of those &amp;gt; 55 years old. Likewise, study participants who had an annual income &amp;lt;$50, 000 or a high school degree or less, had a higher proportion of individuals with partial or no adherence versus those who had an annual income ≥$100, 000 or a college degree or higher. Given the significant differences in adherence by age, income level, and education, consideration of bundled screening (getting multiple screenings during a single visit), especially for some populations, may provide an opportunity to increase complete screening adherence, potentially reducing the number of cancers diagnosed at an advanced stage and increasing survival. Citation Format: Kierstin M. Faw, Jamal R. Winn, Robert A. Smith, Ahmedin Jemal, Parichoy Pal Choudhury, Priti Bandi, Jordan A. Baeker Bispo, Alpa V. Patel. Differences in complete screening adherence across age, income, and education groups [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 7345.
Abstract 6686: Bioinformatic evidence for the involvement of SP1, MYC, and HIF1A in the regulation of miRNAs and histone H2AZ1
Authors: Kotohiko Kimura, Monika Rajput, John Ho Chun, Ru Chih C. Huang
Journal: Cancer Research (2025)

Abstract We previously proposed the concept that the inhibitors for SP1, MYC, and HIF1A should induce strong anticancer activity by reducing the expression of stem cell-related proteins (Curr. Issues Mol. Biol. 2023, 45, 9262-9283). Then, it was shown that in LN229 and U87MG glioblastoma cells, either tetra-methyl-O-nordihydroguaiaretic acid (M4N) or tetra-acetyl-O-nordihydroguaiaretic acid (A4N) suppressed SP1 and only a few stem cell-related proteins and induced only a small amount of cell death while the combination treatment of M4N with A4N greatly suppressed the expression of SP1, MYC, and HIF1A, and all stem cell-related proteins examined, and greatly induced cell death. This data provided the biochemical evidences to support the aforementioned concept. In this study we did bioinformatic analysis to seek for further evidences to support this concept. The ontology analysis showed that the proteins associated with SP1, MYC, and HIF1A were specifically involved in the regulation of transcription and that various miRNAs which had been shown to induce either anti- or pro-cancer activity were associated with SP1, MYC, and HIF1A, which suggested that the inhibition of SP1, MYC, and HIF1A could modulate transcription of both coding and noncoding RNAs and affect cancers. It has been known that nucleosomes, containing histone variants H2AZ1, are important for gene transcription initiation and termination, chromosome segregation and DNA double-strand break repair. The network analysis showed that there were intricate connections between three transcription factors (SP1, MYC, and HIF1A) and H2AZ1. These data overall showed that SP1, MYC, and HIF1A in combination played important roles in transcription regulations via multiple ways (modulations of both coding and non-coding RNAs, miRNAs, and H2AZ1) and that the inhibitions of these transcription factors should have strong negative impacts on cancers which required enhanced production of energy and materials for their rapid proliferation. Thus, these bioinformatic data overall supported our concept as well. Citation Format: Kotohiko Kimura, Monika Rajput, John Ho Chun, Ru Chih C. Huang. Bioinformatic evidence for the involvement of SP1, MYC, and HIF1A in the regulation of miRNAs and histone H2AZ1 [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 6686.
Abstract 6693: Targeting oncogenic miR-135b in colorectal cancer: Computational modeling and small molecule screening for RNA-based therapy
Authors: Berat Demir, Lalehan Oktay, Serdar Durdagi
Journal: Cancer Research (2025)

Abstract Colorectal cancer ranks among the leading causes of cancer-related deaths globally. In this study, we identified miR-135b as a differentially expressed microRNA in colorectal cancer through an analysis of datasets from the Gene Expression Omnibus (GEO) database. Target genes associated with miR-135b were subsequently identified, and pathway and functional enrichment analyses were conducted to provide a deeper understanding of the underlying biological processes. We developed a de novo three-dimensional model of miR-135b's tertiary structure, targeting the Dicer cleavage site for small molecule inhibition. Dicer binds to the terminal loop region of the pre-miRNA and cleaves it to produce a double-stranded miRNA duplex. One strand of this duplex, the guide miRNA, is loaded into the RNA-induced silencing complex (RISC), which mediates miRNA-mRNA interactions, leading to post-transcriptional gene silencing. To identify potential inhibitors, molecular docking simulations were conducted using the ChemDiv miRNA-targeted small molecule library (∼20, 000 compounds). The top-scoring compounds were further explored by screening their commercial analogues in the ZINC library via SwissSimilarity. These analogues were docked at the Dicer cleavage site, and optimized docking scores were obtained. The highest scoring compounds were then subjected to all-atom molecular dynamics simulations, followed by post-simulation analysis to evaluate the dynamic interactions between miR-135b and the selected hit ligands. Citation Format: Berat Demir, Lalehan Oktay, Serdar Durdagi. Targeting oncogenic miR-135b in colorectal cancer: Computational modeling and small molecule screening for RNA-based therapy [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 6693.
Abstract 7087: Sample-sparing immunoassays for early detection of cancer
Authors: Mingyue Wang, Jermaine Brown, Daniel Lee, Salvia Misaghian, Taron Gorham, Leonid Dzantiev, Anu Mathew, Martin Stengelin, Ji Qiu, Karen Anderson, Joshua LaBaer, George Sigal, Jacob Wohlstadter
Journal: Cancer Research (2025)

Abstract Research Use Only (RUO) sample-sparing MULTI-ARRAY immunoassays have been developed for several well-established cancer markers. The primary focus of this project is the development of assays to support research of suspicious lung nodules, but many of these selected markers are also relevant to other cancer types. These immunoassays include a serology panel, two biomarker panels, and a single-marker assay. The serology panel includes assays to detect autoantibodies to p53, CTAG-1, and CTAG-2. This panel requires 25 μL of 2, 500-fold diluted serum or plasma. A biomarker panel requiring 25 μL of 100-fold diluted serum or plasma detects the following biomarkers: CA15-3, SCFR/Kit, ErbB2, IGFBP-2, MIF, MMP-2, MMP-9 (total), REG4, S100A6, and TNF-RI. A second biomarker panel requiring 25 μLof 10-fold diluted serum or plasma detects the following biomarkers: CA125, Ca19-9, CEACAM-5 (CEA), EGFR, VEGFR-1/Flt-1, FLT3L, HE4, MMP-3 (total), and osteopontin. Finally, an assay for the core lung cancer biomarker cytokeratin-19 was developed. All assays had dynamic ranges that span 3-4 logs and are sufficiently sensitive to measure native levels in commercially sourced samples from apparently healthy individuals. The assays were preliminarily evaluated using more than 100 commercially sourced serum or plasma samples from apparently healthy individuals and more than 100 commercially sourced serum or plasma samples from patients with lung or other cancers. Many of the biomarkers had significantly different concentrations in several cancers compared to samples from apparently healthy individuals. These RUO assays may be useful in identifying biomarkers for a multi-marker panel to study early cancer. Citation Format: Mingyue Wang, Jermaine Brown, Daniel Lee, Salvia Misaghian, Taron Gorham, Leonid Dzantiev, Anu Mathew, Martin Stengelin, Ji Qiu, Karen Anderson, Joshua LaBaer, George Sigal, Jacob Wohlstadter. Sample-sparing immunoassays for early detection of 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 7087.
Abstract 6725: Introducing new technology for high performance whole exome sequencing with unparalleled hybridization time flexibility and capability for low to high capture-input
Authors: Daniel Saatman, Jinglie Zhou, Ekaterina Star, Roshani Codipilly, Alexandra Wang
Journal: Cancer Research (2025)

Abstract Whole exome sequencing (WES) via hybridization capture is a targeted sequencing approach to specifically enrich the protein-coding regions of the human genome. The human exome comprises ∼1% of the entire genome but contains the majority of relevant variants for researchers. Targeting this region saves on sequencing costs and data storage while also allowing greater sequencing depth of regions of interest. However, current hybridization capture workflows are challenging to execute in the laboratory due to high-temperature sample and reagent handling, pre-heating of multiple buffers, long hybridization times, and narrow library input ranges. Widening the input range is desirable because it can allow for fewer PCR cycles in library preparation or enable high multiplexing during hybridization capture, the latter of which can lower reagent costs. To evaluate targeted sequencing performance across a wide range of sample inputs and hybridization times, we used low to high total input—1-plex 100ng to 12-plex 6000ng—and hybridized for as short as 1 hour up to overnight. We used the Integrated DNA Technologies (IDT) novel xGen™ Hybridization and Wash v3 kit, which features a user-friendly workflow without hot-liquid handling or temperature-sensitive urgency. This performance is benchmarked side-by-side with a current commercial hybridization-capture kit. Using these methods, we achieve similar targeting, coverage, uniformity, and GC-balance across all samples with minimal impact from low inputs and short hybs. Further, we calculated the reference/alternate (ref/alt) allelic fraction and found no considerable differences between capture conditions, indicating the potential of this workflow for genotyping applications with low-input samples and/or short hybridizations. This flexibility in hybridization time and library input along with the streamlined workflow allows researchers to meet diverse experimental demands and effectively capture the human exome. Citation Format: Daniel Saatman, Jinglie Zhou, Ekaterina Star, Roshani Codipilly, Alexandra Wang. Introducing new technology for high performance whole exome sequencing with unparalleled hybridization time flexibility and capability for low to high capture-input [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 6725.
Abstract 6719: GULP1 knockout promotes carcinogen-induced bladder cancer by regulating the NRF2-KEAP1 signaling axis
Authors: Chonji Fukumoto, Naveen C. Pandey, Sylvia S. Sanchez, Pritam Sadhukhan, Christopher M. Koenig, Susmitha R. Pagadala, Fenna C. Sillé, Mohammad O. Hoque
Journal: Cancer Research (2025)

Abstract Urothelial carcinoma of bladder (UCB) is the ninth most commonly diagnosed cancer worldwide. Some key genetic and epigenetic alterations are hallmarks on the initiation and progression of UCB. The nuclear factor E2-related factor 2 (NRF2)-Kelch-like ECH-associated protein-1 (KEAP1) signaling pathway, essential for detoxifying reactive oxygen species, is normally regulated by the interaction of NRF2 with KEAP1and the actin cytoskeleton in the cytoplasm. However, genetic and epigenetic alterations can lead to a constitutive activation of NRF2 through the loss of KEAP1 function. This dysregulation results in NRF2 translocation to the nucleus, triggering the expression of numerous genes. We recently reported that phosphotyrosine binding (PTB) domain-containing engulfment adaptor protein 1 (GULP1) is frequently silenced in UCB by promoter hypermethylation, and interacts with the KEAP1-actin cytoskeleton complex to regulate NRF2. Furthermore, the loss of GULP1 expression led to uncontrolled NRF2 signaling, driving cancer progression and resistance to chemotherapy. Here, to strengthen our previous findings that GULP1 acts as a tumor suppressor gene (TSG) in UCB, we exposed GULP1 knockout (KO) mice to a most commonly used carcinogen for generating UCB model in mice. To this end, we exposed 4-week-old GULP1 KO and wild type (WT) C57BL/6 mice to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 6 to 20 weeks. We then analyzed the resulting bladder tumors using various methods to investigate the NRF2-KEAP1 axis, tumor subtype, and several tumor immune microenvironment (TIME) factors. Our data demonstrates that GULP1 KO exhibits a higher frequency of carcinogen-induced UCB and muscle invasion compared to WT counterparts via regulating the NRF2-KEAP1 axis. Furthermore, GULP1 KO carcinogen-induced tumors appear at earlier time point compared to WT mice. Interestingly, GULP1 KO mice exhibited a characteristic subtype and TIME dynamics that differed from those of WT. In conclusion, our pilot in vivo data suggested that GULP1 may regulate the NRF2-KEAP1 signaling pathway in UCB. Further experiments are ongoing to understand the comprehensive mechanisms of GULP1 involvement in UCB and its association with chemo and immunotherapy response. Citation Format: Chonji Fukumoto, Naveen C. Pandey, Sylvia S. Sanchez, Pritam Sadhukhan, Christopher M. Koenig, Susmitha R. Pagadala, Fenna C. Sillé, Mohammad O. Hoque. GULP1 knockout promotes carcinogen-induced bladder cancer by regulating the NRF2-KEAP1 signaling axis [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 6719.
Abstract 6727: Ecdysoneless (ECD) as a key estrogen-regulated protein driving progression in ER-positive breast cancer
Authors: Farshid Oruji, Asher Rajkumar Rajan, Mohsin Raza, Bhopal Mohapatra, Hamid Band, Vimla Band
Journal: Cancer Research (2025)

Abstract Background: Breast cancer (BC) is a heterogenous disease, with estrogen receptor-positive (ER+) BC accounting for over 70% of cases. ER+ BC depend on estrogen signaling for oncogenesis and metastasis. Even though treatments targeting ER pathway have improved patient’s outcome, factors driving ER+ BC progression particularly in metastatic remain unclear. One of these factors is Ecdysoneless (ECD), a highly conserved protein from yeast to human. ECD expression correlates with ER expression, ECD overexpression is observed in ER+ BC and ECD overexpression correlates with poor patient survival. In this study, we assessed the relationship of ECD and ER, and the role of ECD in ER+ BC oncogenic traits. Methods: Bioinformatic analysis of publicly available datasets were explored for the relationship between ER and ECD and survival analysis was performed to examine the link between ECD, ER, and ER target MYC expression. ECD promoter analysis followed by chromatin immunoprecipitation (ChIP) and promoter-luciferase assays were used to assess estrogen-dependent ER recruitment to the ECD promoter. Estradiol (E2) treatments were performed to examine how estrogen signaling affects ECD levels. The effects of ECD overexpression were performed in ER+ breast cancer cells to evaluate changes in in vitro tumorigenic traits. Results: ECD expression correlated with ER levels in publicly available datasets. Survival data showed patients with elevated levels of ECD in ER+ BC had worse outcome. The ECD promoter contained estrogen response elements, and ChIP assays confirmed E2 mediated recruitment of ER to the ECD promoter. E2 treatment enhanced ECD promoter-luciferase activity. Overexpression of ECD in ER+ cells enhanced oncogenic traits. Conclusions: We have identified ECD is a novel estrogen regulated protein that plays a critical role in ER-driven oncogenesis in ER+ BC. Current studies are exploring the role of overexpressed ECD in in vivo preclinical mice models and therapy resistance. Citation Format: Farshid Oruji, Asher Rajkumar Rajan, Mohsin Raza, Bhopal Mohapatra, Hamid Band, Vimla Band. Ecdysoneless (ECD) as a key estrogen-regulated protein driving progression in ER-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 6727.