tbuckley/cabot-search huggingface dataset:
Abstract 3818: Climate stressors and oncology care: awareness of healthcare professionals in Puerto Rico
Authors: Jessica Hernandez Marrero, Nancy R. Cardona-Cordero, Marievelise Soto-Salgado, Pamela Ginex, Milagros Eliah, Ana P. Ortiz
Journal: Cancer Research (2025)

Abstract Introduction: Climate change affects oncology care and health outcomes of cancer patients. Island communities are particularly vulnerable to these climate-related hazards and healthcare disruptions. Oncology healthcare professionals (OHP) are called to participate in climate change education and adaptation efforts actively. We investigate the awareness of OHP in Puerto Rico regarding the impact of climate change on oncology care. Methodology: This ongoing cross-sectional study is recruiting adult OHPs. The “Global Survey of the Effects of Climate Change on Oncology Care” was translated into Spanish and is being administered as a data collection instrument. OHP are being recruited online using a quick-response (QR) code, social media, and through in-person activities, including oncology medical and nursing annual meetings. Descriptive statistics are used to define the study population. From Aug-Nov 2024, 178 OHP completed the survey; 101 (56.7%) are used in this analysis as they properly completed questions related to the impact of atmospheric events on oncology care and climate-related events experienced by patients reported by OHP. Results: Most study participants were nurses (52.5%), followed by physicians (31.7%) and other healthcare professionals (15.8%); 79% worked in urban settings. The climate events most reported to affect oncology care were hurricanes (91.0%), floods (86.1), heavy rains (85.1%), and extreme heat (71.3%). Most OHP reported that due to atmospheric events, patients have frequently/occasionally missed appointments (85.2%), experienced delays in treatments (75.2%), needed relocation for treatment (46.5%), had climate-related health concerns (74.2%), had mental health (80.2%) and issues (77.2%) issues, and had concerns about food security or housing (65.4%). In terms of preparedness, 54.5% of OHP reported that their workplace had disaster plans and 82.2% that their institutions are taking preparation steps for climate-related events. Conclusion: While our sample of OHP exhibits awareness of the impact that climate change can pose on oncology care, many did not report planning efforts in their institutions. Education and preparedness efforts among OPH are warranted. Funding: NIH awards U54GM133807; 2U54MD007587; P20CA294096-01 Citation Format: Jessica Hernandez Marrero, Nancy R. Cardona-Cordero, Marievelise Soto-Salgado, Pamela Ginex, Milagros Eliah, Ana P. Ortiz. Climate stressors and oncology care: awareness of healthcare professionals in Puerto Rico [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 3818.
Abstract 1835: The impact of artemin depletion on acute radiation-associated oral pain
Authors: Faihaa A. Ahmed, Thitsana Ingkasri, Sophi Schofield, Elizabeth Wright, B. Duncan X. Lascelles, Santosh K. Mishra, Michael Nolan
Journal: Cancer Research (2025)

Abstract A common complication of therapeutic radiotherapy for head and neck cancer is the development of severe pain. The biological mechanisms underlying acute orofacial radiation-associated pain (RAP) are unknown but may involve cold-sensing and cold-signaling pathways. A key cold receptor is TRPM8 (Transient Receptor Potential Melastatin family member 8), whose activation might be mediated by the neurotrophic factor artemin (ARTN) acting on its primary receptor, GFRα3. To test the hypothesis that radiation triggers release of ARTN, which results in activation of TRPM8 to cause RAP, we performed tongue-irradiation in mice that had been treated with either monoclonal anti-ARTN-neutralizing antibody or control (IgG). Lingual ARTN expression (IHC) increased after lingual irradiation, and this was mitigated by anti-ARTN treatment. Assessments of glossitis severity, body weight, and behavioral pain measures indicated that irradiation caused severe pain, which ARTN depletion failed to mitigate. However, after topical ophthalmic application of cold saline solution, tongue-irradiated anti-ARTN treated mice wiped their eyes less than their IgG-treated counterparts, and as assessed via ex vivo calcium imaging of trigeminal ganglia neurons, their afferent sensory nerves were less responsive to cold buffer. We therefore conclude that at the molecular level, ARTN depletion reduced radiation-induced cold sensitivity, but was insufficient to reduce behavioral indicators of RAP. Ongoing work in tissues from these mice is exploring whether changes in cold sensitivity correlated with TRPM8 expression, and future experiments are planned to assess: (1) whether genetic deletion of ARTN reduces RAP, and (2) if modulation of ARTN leads to upregulation of alternative TRPM8 activators. Citation Format: Faihaa A. Ahmed, Thitsana Ingkasri, Sophi Schofield, Elizabeth Wright, B. Duncan X. Lascelles, Santosh K. Mishra, Michael Nolan. The impact of artemin depletion on acute radiation-associated oral pain [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 1835.
Abstract 2754: Long-read direct RNA sequencing identifies m3C modification sites in poly(A) RNAs from pancreatic cancer cells
Authors: Kenzui Taniue, Shuhei Mitsutomi, Anzu Sugawara, Kenji Takahashi, Yusuke Mizukami, Nobuyoshi Akimitsu
Journal: Cancer Research (2025)

Abstract Covalent modifications provide a precise and effective mechanism to regulate the biogenesis, stability, and function of biological molecules, including DNA, RNA, proteins, and lipids. More than 300 distinct chemical modifications have been identified in both coding and non-coding RNAs, forming a diverse RNA modification landscape known as the epitranscriptome. RNA modifications are mediated by three classes of proteins: writers, which add modifications; erasers, which remove them; and readers, which recognize and interpret modified RNAs. RNA modifications play critical roles in cell homeostasis and cell developmental processes by regulating gene expression, RNA metabolism, and translation into proteins. Dysregulation of RNA modifications has been linked to the pathogenesis of various human diseases, including cancer. Recent studies has shown that 3-methylcytidine (m3C) is primarily located at position 32 on the anticodon loop of certain transfer RNAs (tRNAs). This modification is catalyzed by m3C writers, such as METTL2A, METTL2B, METTL6, and METTL8. These writers and their cofactors have been associated with human diseases. m3C has also been detected in polyadenylated RNA (poly(A) RNA) at levels approximately 1000-fold lower than in tRNA through LC-MS/MS analysis. However, its transcriptome-wide distribution and functions remain unknown due to its low abundance and the absence of commercially available anti- m3C antibodies suitable for immunoprecipitation. Here, we demonstrated that METTL2A expression is upregulated in pancreatic tumor tissues and that high METTL2A levels are associated with poor prognosis in pancreatic cancer patients. To further investigate the role of METTL2A, we performed comparative direct RNA sequencing on the pancreatic cancer cell line AsPC-1 to identify potential METTL2A-mediated m3C sites in poly(A) RNA. These m3C sites were enriched in the CC motif and predominantly located in the coding sequences of mRNA, mitochondrial mRNA, and mitochondrial ribosomal RNA. Moreover, METTL2A downregulated m3C RNAs and altered the balance between specific isoforms containing METTL2A-mediated m3C sites by promoting exon inclusion and shifting isoform expression, underscoring a potential role of m3C in poly(A) RNA in regulating gene expression. In conclusion, our approach may contribute to uncovering the functions and characteristics of previously unknown RNA modifications regulated by various factors. Citation Format: Kenzui Taniue, Shuhei Mitsutomi, Anzu Sugawara, Kenji Takahashi, Yusuke Mizukami, Nobuyoshi Akimitsu. Long-read direct RNA sequencing identifies m3C modification sites in poly(A) RNAs from pancreatic cancer 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 2754.
Abstract 1456: Tumor lineage plasticity blockade by therapeutic targeting of an epigeneticregulator
Authors: Xiong Zhang, Yatian Yang, Eva Corey, Hongwu Chen
Journal: Cancer Research (2025)

Abstract Tumor lineage plasticity (LP) is an emerging hallmark of cancer progression in solidtumors, such as prostate cancer, pancreatic cancer and lung cancer. However, theexact molecular mechanisms that drive the aberrant LP programs remain poorlydefined. Here we identified bromodomain protein BRD4 as a crucial player. BRD4knockdown and its inhibitors potently suppressed the LP programs both in vitro and invivo. Integrated ChIP-seq and RNA-seq analysis of tumors revealed that BRD4 drivesLP by increasing local chromatin accessibility and directly activating LP gene programswhich includes neurogenesis, axonogenesis and stem cells and key drivers such asBRN2, ASCL1/2, SOX2, SOX9 and RUNX1/2. Significantly, we demonstrated thatBRD4 inhibitor AZD5153, currently at clinical development, possesses potent activity inalmost complete blockade of tumor growth of both de novo neuroendocrine prostatecancer (NEPC) and treatment-induced NEPC PDXs. Further study revealed thatsuppression of tumor expression of LP programs through reduction of local chromatinaccessibility is a primary mechanism of action (MOA) by AZD5153. Together, ourfindings demonstrated that BRD4 plays a fundamental role in directly activating tumorLP programs and that its inhibitor AZD5153 is highly promising in effective treatment ofthe lethal forms of the diseases. Citation Format: Xiong Zhang, Yatian Yang, Eva Corey, Hongwu Chen. Tumor lineage plasticity blockade by therapeutic targeting of an epigeneticregulator [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 1456.
Abstract 3848: Smoking promotes angiogenesis and epithelial to mesenchymal transition in breast cancer
Authors: Venkat Katkoori, Shreeya R. Kandukuri, Madhukar V. Burra, James E. Trosko, Deimante M. Tamkus, Cherly Leece, Lakshimipathi R. Kareti, George S. Abela, Harvey L. Bumpers
Journal: Cancer Research (2025)

Introduction: Nicotine, the addictive component of cigarettes, induces tumor progression via the α7-nicotine acetylcholine receptor (α7-nAChR) subtype in lung cancer. However, the molecular mechanisms by which nicotine impacts tumor progression of breast cancer (BC) remain unclear. In this study, we evaluated the effects of nicotine/smoking on tumor angiogenesis, and epithelial-mesenchymal transition (EMT) signaling mechanisms that are involved in BC progression. Experimental Design: BC cell spheroids from the MCF7, a non-invasive cell line was treated with nicotine (0.3 to 3μM) for 14 days. Sections of tumor tissue from the human BC (smoking vs. never smoking) were assessed for phenotypic expressions of α7-nAChR, and vimentin by immunostaining (IHC). CD31 staining was used to evaluate tumor angiogenesis, as measured by microvessel density (MVD). Western blot (WB) analyses were also performed on lysates of both cell lines and tumors to assess the effect of nicotine on the signaling pathways that promote BC progression. Results: The present study revealed that nicotine treated spheroids have increased expression of Ki67, Mdr1, Oct4 signatures that are indicative of BC progression. IHC analysis indicated that tumor from patients that smoked displayed increased expression of α7-nAChR. Furthermore, the expression of Oct4 (marker for cancer stem-cell), and vimentin (marker for EMT) that correlates with advanced disease and metastasis were found to be higher in smokers. However, tumors from non-smokers had low expression of Oct4 and vimentin. It was also found that tumors from patients who smoked had well established vascularity, while tumors from non-smokers had very little vascularization. Indeed, the mean MVD was lower in tumors from non-smokers compared to tumors from smokers. Conclusions: These findings offer significant novel insights into the mechanism by which nicotine contributes to the increased aggressiveness of BC. This work was supported in part by NIH/NCI Workforce Diversity Grant R21-CA171251. Citation Format: Venkat Katkoori, Shreeya R. Kandukuri, Madhukar V. Burra, James E. Trosko, Deimante M. Tamkus, Cherly Leece, Lakshimipathi R. Kareti, George S. Abela, Harvey L. Bumpers. Smoking promotes angiogenesis and epithelial to mesenchymal transition in 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 3848.
Abstract 1527: Reversal of the Warburg Effect with BPM31510 treatment in a quinone deficient C6 Glioma resulting in efficacy
Authors: Michael A. Kiebish, Abbas Khojasteh, Sylwia Stopka, Juan J. Aristizabal-Henao, Seema Nagpal, Lisa Ghiglieri, Mustafa Kendirli, Maria-D Nastke, Stephane Gesta, Niven R. Narain, Vijay Modur, Lawrence Recht
Journal: Cancer Research (2025)

Abstract BPM31510-IV is a drug-lipid conjugate nanodispersion comprised of oxidized Coenzyme Q10 (CoQ10) in clinical development for glioblastoma multiforme (GBM). BPM31510 reengineers tumor metabolism, while supporting efficient metabolism of non-tumorigenic tissue. Recent evidence suggests that GBM tumors have a deficiency in quinones, most notable CoQ10, leading to altered mitochondrial function. Additionally, emerging data suggests that the rat C6 glioma also is deficient in quinone metabolites. Herein, we explored the therapeutic MOA of BPM31510 in the treatment of GBM based on twice a day dosing vs intermittent dosing. Survival assessment was performed with untreated, 100 mg/kg BID dosing (IP), 200 mg/kg IV dosing (every other day) and 400 mg/kg IV dosing (every other day) in rats implanted with a C6 glioma. Tumor implantation was confirmed using MRI at day 9 and treatment began at day 11. In a parallel treatment study, rats were treated in a corresponding manner and tissue samples were collected at day 14. Rat brains were immediately frozen and were assessed by spatial metabolomics/lipidomics and quinone assessment (quinomics) to spatially resolve metabolic changes at a single cell level post-treatment. C6 glioma exhibited a deficiency in CoQ9 (dominant CoQ in rats) and treatment with BPM31510 was able to increase CoQ9 in tumors reengineer metabolic activity, thus reversing the Warburg effect. Analysis of BPM31510 treated animals revealed a dose dependent and dosing sequent dependent response impacting survival and tumor resolution as well as an impact on spatial metabolic effect of BPM31510 treatment in brain compared to C6 glioma tissue. Additionally, changes in lactate and citrate were also evident in tumor compared to brain in a dose and cycling dependent manner, which demonstrates reengineering of mitochondrial metabolism in cancer compared to normal brain. These data definitely demonstrate that BPM31510 is capable of entering the brain and tumor, reengineering mitochondrial metabolism resulting in a resolution of the glioma which impacts survival. Both dosing and sequencing of doses impact outcome and metabolic response. Citation Format: Michael A. Kiebish, Abbas Khojasteh, Sylwia Stopka, Juan J. Aristizabal-Henao, Seema Nagpal, Lisa Ghiglieri, Mustafa Kendirli, Maria-D Nastke, Stephane Gesta, Niven R. Narain, Vijay Modur, Lawrence Recht. Reversal of the Warburg Effect with BPM31510 treatment in a quinone deficient C6 Glioma resulting in efficacy [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 1527.
Abstract 5572: The transcription factor hepatic leukemia factor (HLF): a potential therapeutic target in triple negative breast cancer
Authors: Ibrahim Bouakka, Marine Sirerol, Aymeric Silvin, Alicia Tran-Dien, Anna Rocca, Fabrice Andre
Journal: Cancer Research (2025)

Abstract Pivotal role of immune response in the evolution of triple negative breast cancer has been largely reported in the last decade. Our previous study highlighted the role of HLF gene as part of a four gene signature and was found to be negatively correlated with tumoral immune cells infiltration. We investigated more precisely its implication in the immune response and TNBC tumor development. Bioinformatics analysis of publicly available TNBC patient datasets revealed that in mesenchymal tumor subtypes expressing low levels of HLF upregulation of genes associated with neutrophil attraction and activation pathways was observed in comparison with those expressing high HLF levels. The implication of neutrophils in cancer is contentious as they can function either as active anti tumoral partners or as pro tumoral agents promoting immunosuppression and tumor growth. This ambiguity stems from their high plasticity which enables them to switch roles during tumor progression influenced by signals from tumoral microenvironment in particular those from surrounding tumor cells. In this study we employed CRISPR Cas9 technology to inactivate the HLF gene in TNBC cell lines enabling us to elucidate the downstream effects on the chemokine and protease inhibitor landscape that governs neutrophil infiltration and function within the microenvironment of TNBCs especially in mesenchymal subtypes. In vivo experiments using immunodeficient mouse models revealed that HLF downregulation in TNBC mesenchymal subtypes correlates with increased neutrophil infiltration into the tumor leading to inhibit tumor growth. Altogether our results suggest that a reduction of HLF expression can lead in the early steps of tumor development to the awakening of the anti tumoral function of neutrophils to enforce the necessary immunological tone to tumor elimination. Thus HLF emerges as a potential therapeutic target in order to favor infiltration and function of anti tumoral neutrophils to restore an efficient immune response in the aggressive mesenchymal TNBC subtype. Citation Format: Ibrahim Bouakka, Marine Sirerol, Aymeric Silvin, Alicia Tran-Dien, Anna Rocca, Fabrice Andre. The transcription factor hepatic leukemia factor (HLF): a potential therapeutic target in triple negative 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 5572.
Abstract 1453: Investigating the Role of FOXO4 in glioblastoma
Authors: Megan Keniry, David Uribe
Journal: Cancer Research (2025)

Abstract Evolutionarily conserved partially redundant Forkhead box transcription factors FOXO -1, -3, and -4 drive stem cell maintenance in embryonic, cancer, mesenchymal, hematopoietic, and neural stem cells. Canonically, high PI3K output leads to cytoplasmic/inactive FOXO factors. Stem cells, however, are fundamentally rewired to have high PI3K Pathway activity and nuclear/active FOXO factors. Our previously published work and the work of others show that FOXO factors directly bind to and activate stem genes in both embryonic stem cells and the poor prognosis of cancer glioblastoma multiforme (GBM) to drive stem cell fate. However, the precise mechanisms utilized by FOXO transcription factors in driving stemness, hindering differentiation, and promoting cancer are incompletely understood. To gain insight into the role of nuclear FOXO4 in glioblastoma, we disrupted the gene encoding this factor using CRISPR Cas9 genome editing and performed RNA-seq in the U87MG background. We identified 2, 519 differentially expressed genes in FOXO4-deleted U87MG cells compared to unmodified controls, including those that drive invasion. Current work is examining whether FOXO4 promotes invasion of glioblastoma cells. Citation Format: Megan Keniry, David Uribe. Investigating the Role of FOXO4 in glioblastoma [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 1453.
Abstract 4229: GTA182: A potentially best-in-class, MTA-cooperative PRMT5 inhibitor for MTAP-deleted advanced solid tumors
Authors: Weifeng Mao, Bing Yao, Yanfeng Zhou, Wei Liu, Xiangping Zhang, Minghua Wang, Yingqi Hua, Wei Sun, Haoran Mu, Yining Tao, Qi Zhang, Mai Le, Corrine Zeng, Xiao-Hui Gu, Mingxi Li, James Joseph, Fred Aswad
Journal: Cancer Research (2025)

Background: GTA182 is a second-generation, MTA-cooperative PRMT5 inhibitor developed to selectively target MTAP-null tumors, where MTAP deletion (often co-occurring with CDKN2A loss) creates a synthetic lethal vulnerability. Unlike first-generation inhibitors, GTA182 is optimized for high selectivity in MTAP-deleted versus MTAP wild-type cells, dose-proportional exposure, and CNS penetration, positioning it as a potential best-in-class treatment. GTA182 is currently in phase 1 clinical trials for advanced solid tumors with homozygous MTAP deletion. Methods: Using structure-based design and advanced molecular modeling, GTA182 was optimized for enhanced ADME-PK properties, achieving broad systemic and CNS exposure. Preclinical selectivity and anti-tumor efficacy were evaluated in both MTAPwt and MTAP-null tumor models, with comparisons made against existing second-generation PRMT5 inhibitors. Results: GTA182 demonstrated over 100-fold selectivity for MTAP-null cells, with strong anti-tumor efficacy at 3 mg/kg, substantially outperforming competitor compounds. Additionally, GTA182’s optimized dose-proportional exposure profile resulted in a 30-fold multiple of exposure, with a therapeutic index up to 23-fold in murine mouse models, supporting its favorable safety margin and once-daily dosing. Effective blood-brain barrier penetration, exemplified by high Kp,uu and robust activity in the orthotopic U87 glioblastoma model, further supports its potential to treat CNS malignancies. Preliminary combination data with PD-1 inhibitors in MTAP-null osteosarcoma models suggest promising synergy, reinforcing GTA182’s versatility and potential best-in-class status. Conclusion: GTA182 represents a highly selective, MTA-cooperative PRMT5 inhibitor with significant preclinical efficacy and a broad therapeutic window. GTA182 is now advancing through phase 1 trials with the aim to establish safety, pharmacokinetics, and efficacy in MTAP-deleted advanced tumors. With the potential to safely address both CNS and non-CNS malignancies, GTA182 is positioned to emerge as a differentiated therapeutic in precision oncology. Citation Format: Weifeng Mao, Bing Yao, Yanfeng Zhou, Wei Liu, Xiangping Zhang, Minghua Wang, Yingqi Hua, Wei Sun, Haoran Mu, Yining Tao, Qi Zhang, Mai Le, Corrine Zeng, Xiao-Hui Gu, Mingxi Li, James Joseph, Fred Aswad. GTA182: A potentially best-in-class, MTA-cooperative PRMT5 inhibitor for MTAP-deleted advanced solid 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 4229.