tbuckley/cabot-search huggingface dataset:
Abstract 727: Association of baseline tumor and peripheral biomarker features with efficacy in metastatic castration-resistant prostate cancer patients treated with xaluritamig
Authors: Benjamin E. Decato, Zhao Yang, Isabelita Vengco, Katherine Paweletz, Amrita Pati, Anita Reddy, Tara O'Donohue, Sheryl Treichel, Kristen M. Smith
Journal: Cancer Research (2025)

Abstract Xaluritamig, a novel STEAP1 x CD3 XmAb® 2+1 T-cell engager, is showing initial safety and efficacy in patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report on the association of baseline tumor and peripheral biomarker characteristics with efficacy in the first-in-human dose exploration trial. We examined STEAP1 target expression by immunohistochemistry in fresh and archival tumor biopsies, peripheral immune populations by multiparameter flow cytometry, and tumor somatic mutations via circulating tumor DNA (ctDNA) in plasma. STEAP1 was broadly expressed in mCRPC subjects with greater than 95% of tumor biopsies containing at least 1% STEAP1-positive tumor cells. STEAP1 expression was similar at various metastatic sites examined in the patient cohort and was not impacted by the number or types of prior therapies. Additionally, STEAP1 expression levels were not correlated with PSMA expression. Neither STEAP1 IHC intensity nor the percentage of STEAP1-positive tumor cells correlated with response to xaluritamig. Baseline peripheral immune cell populations and blood chemistry features may potentially associate with response. Patients who achieved a PSA50 response had lower neutrophil counts, neutrophil-to-lymphocyte ratio, and C-reactive protein than non-responding patients. The association between xaluritamig response and baseline tumor T cell infiltration is being assessed. Baseline somatic tumor mutations were determined by analysis of ctDNA. The distribution of somatic tumor mutations was consistent with published mCRPC mutational frequencies, with deleterious alterations in TP53, AR, PTEN and RB1 observed most frequently. Xaluritamig efficacy was observed in patients whose tumors carried these common mCRPC alterations, as well as in patients with detectable TMPRSS2:ERG fusions Taken together, these data suggest that xaluritamig has anti-tumor activity in a broad mCRPC patient population and provide support for enrolling patients with mCRPC in a Phase 3 study of xaluritamig (NCT06691984) regardless of STEAP1 expression levels or tumor mutational status. Citation Format: Benjamin E. Decato, Zhao Yang, Isabelita Vengco, Katherine Paweletz, Amrita Pati, Anita Reddy, Tara O'Donohue, Sheryl Treichel, Kristen M. Smith. Association of baseline tumor and peripheral biomarker features with efficacy in metastatic castration-resistant prostate cancer patients treated with xaluritamig [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 727.
Abstract 887: Human microRNA-1250-5p targets IGFBP2 expression to regulate NK cell proliferation in hypoxia
Authors: Kyung-Mi Lee, None Minwha shin, Seon Ah Lim
Journal: Cancer Research (2025)

Abstract Insulin-like growth factor binding protein 2 (IGFBP2) is involved in many physiological events, such as progression and survival of many types of cells. However, little is known about its role in human natural killer (NK) cells. Here, we report that miR-1250-5p regulates IGFBP2 expression, the most expressed gene in hypoxia-activated NK cells, thereby promotes NK cell proliferation in hypoxia. We found that IGFBP2 was not only highly expressed in cellular level, but also secreted from NK cells exposed to hypoxia. Both endogenous and secreted IGFBP2 are involved in NK cell proliferation in hypoxia. We identified miR-1250-5p directly binds to the 3’untranslated region of IGFBP2, and negatively regulates the expression of IGFBP2 in hypoxia-activated NK cells. Overexpression of miR-1250-5p has decreased NK cell proliferation, whereas inhibition of miR-1250-5p shows dramatically opposite effect. Clinical data showed that IGFBP2 expression was increased in tumor infiltrating NK cells compared with non-tumor infiltrating NK cells in patients of hepatocellular carcinoma (HCC), which is one of the representative tumors of hypoxia. We further demonstrated that miR-1250-5p negatively regulates IGFBP2 expression in tumor infiltrating NK cells of HCC patients. Furthermore, proliferation and survival markers, Ki-67, PCNA, cIAP1, cIAP2 as well as NK cell activating receptor, NKp44, were upregulated, whereas apoptotic and senescence markers, Bax, p53 and p16 were downregulated in tumor infiltrating NK cells in patients of HCC. These results indicate that the proliferation of NK cells in hypoxia is regulated by miR-1250-5p and its target gene IGFBP2, thereby enhancing therapeutic potential of NK cells against hypoxic tumor microenvironment. Citation Format: Kyung-Mi Lee, Minwha shin, Seon Ah Lim. Human microRNA-1250-5p targets IGFBP2 expression to regulate NK cell proliferation in hypoxia [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 887.
Abstract 1041: Active interception to modulate the systemic cancer-permissive microenvironment and reduce cancer incidence in companion dogs with elevated cancer risk
Authors: Ashley J. Schulte, Rose Dicovitsky, Taylor A. DePauw, Amber L. Winter, Kathleen L. Stuebner, Andrea Chehadeh, Sara Pracht, Antonella Borgatti, Ali Khammanivong, Mitzi Lewellen, Lauren E. Burt, Daniel A. Vallera, Michael S. Henson, Erin B. Dickerson, Christopher Ober, Kari L. Anderson, Esther Nell, Aaron L. Sarver, Gary R. Cutter, Jaime F. Modiano
Journal: Cancer Research (2025)

Abstract Companion dogs have a lifetime cancer risk similar to that of humans. This excess risk, as compared to what is seen in other species, seems to be due to our recent success in outliving our evolutionarily adapted lifespan. For cancers to develop, a cancer-permissive environment must be present, which may exist months or even years before a tumor becomes detectable. We have developed the Shine On Suspicion (SOS) test, a flow cytometry based test to detect these changes that lead to a cancer-permissive environment. To make this test actionable, we combined it with a novel agent for cancer interception (secondary prevention) called eBAT. eBAT is a bispecific ligand targeted toxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment of urokinase. This drug was designed to use epidermal growth factor receptors (EGFR) and urokinase-type plasminogen receptors (uPAR) as baits to deliver the lethal toxin into the cells, rather than disrupting receptor signaling. eBAT has self-limiting, well-tolerated side effects and is safe enough for administration to otherwise healthy individuals. To date, eBAT has been administered to 11 healthy dogs that were determined to have elevated cancer risk based on the SOS test, with only 1 of the 11 dogs developing cancer more than 2 years after treatment. A hazard ratio calculated with a 95% confidence interval shows that dogs receiving eBAT interception had nearly 4 times reduction in risk of a cancer diagnosis compared to controls. Ongoing research aims to explore the identity and function of niche-forming cells to improve cancer prevention strategies and their applicability to humans. Citation Format: Ashley J. Schulte, Rose Dicovitsky, Taylor A. DePauw, Amber L. Winter, Kathleen L. Stuebner, Andrea Chehadeh, Sara Pracht, Antonella Borgatti, Ali Khammanivong, Mitzi Lewellen, Lauren E. Burt, Daniel A. Vallera, Michael S. Henson, Erin B. Dickerson, Christopher Ober, Kari L. Anderson, Esther Nell, Aaron L. Sarver, Gary R. Cutter, Jaime F. Modiano. Active interception to modulate the systemic cancer-permissive microenvironment and reduce cancer incidence in companion dogs with elevated cancer risk [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 1041.
Abstract 1074: CTCFDB: a systematic framework and comprehensive data resource for CTCF binding in the human genome
Authors: Shengyuan Wang, Zhenjia Wang, Grant Atwood, Yanbin Xu, Chongzhi Zang
Journal: Cancer Research (2025)

Abstract CCTCC-binding factor (CTCF), a highly conserved zinc finger protein, plays a crucial role in the three-dimensional (3D) genome organization by mediating DNA loops and topologically associating domains (TADs). Variations in CTCF binding across different cell types can lead to changes in cell type-specific chromatin conformation, altering gene expression and contributing to diseases such as cancer. Despite its importance, an up-to-date and comprehensive database for human CTCF binding sites has been lacking. To fill this gap, we developed CTCFDB, a curated data resource encompassing 2, 251 high-quality CTCF ChIP-seq datasets from NCBI GEO across 344 human cell types. We identified 510, 675 high-confidence CTCF binding sites in the human genome. Among those, 22, 722 were charactered as constitutive binding sites that are conserved across cell types. Using binding profiles across high-confidence CTCF binding sites, we performed unsupervised clustering analyses on all samples and found that the majority of cell types were clustered together, indicating cell type-specific binding patterns. Besides, we characterized 65, 697 cell type-specific gained and 18, 990 lost CTCF sites by focusing on individual union sites, further demonstrating the cell type specificity of CTCF binding. CTCFDB, with its systematic approach and user-friendly interface, provides an invaluable resource for advancing research on 3D genomics and gene regulation. This framework can be extended to generate similar data resources for other DNA-associating proteins, facilitating broader insights into functional genomics and cancer research. Citation Format: Shengyuan Wang, Zhenjia Wang, Grant Atwood, Yanbin Xu, Chongzhi Zang. CTCFDB: a systematic framework and comprehensive data resource for CTCF binding in the human genome [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 1074.
Abstract 121: Iqgap3 and Myc interaction regulates damaged stomach repair and early gastric carcinogenesis
Authors: Junichi Matsuo, Mitsuhiro Shimura, Jungwon Lee, Linda S. Chuang, Wei Peng Yong, Yoshiaki Ito
Journal: Cancer Research (2025)

Abstract The gastrointestinal tract is frequently subjected to tissue damage caused by various environmental stressors. Adult stem cells conduct tissue repair through regenerative programs with striking parallels to carcinogenesis, implying that dysregulated repair mechanisms initiate cancer development. Previously, we identified Iqgap3 as a marker of rapidly proliferating stem cells within the isthmus of gastric glands, a region essential for maintaining tissue homeostasis. Following tissue injury, we observed upregulation of Iqgap3 expression and activation of Myc signaling pathways, particularly within the fully differentiated chief cell population. Given that Myc is a major oncoprotein, our findings implicate Iqgap3 as a critical mediator in the stomach repair process and carcinogenesis. To understand how the role of Iqgap3 in tissue repair may be hijacked for carcinogenesis, we developed a conditional knockout (cKO) mouse model that attenuates Iqgap3 expression in gastric epithelial cells. Tissue damage and Iqgap3 deletion were induced by high-dose tamoxifen (HDT) treatment. Iqgap3-cKO mice were markedly compromised in tissue repair, exhibiting reduced cellular proliferation and chief cell population even one month after tissue injury. Transcriptomic analyses revealed that Iqgap3 deficiency suppressed the Myc signaling pathway and stem cell activity in the stomach, indicating a causal link between Iqgap3 and Myc during tissue regeneration. Furthermore, Iqgap3 depletion in oncogenic KrasG12D-induced metaplasia mouse model and KrasG12D-induction with Apc-depleted dysplasia mouse model protected against formation of metaplasia and dysplasia. Mechanistically, Iqgap3 deficiency led to reduced expression of neoplastic factors, such as CD44, Aqp5 and Trop2. Interestingly, Myc phosphorylation was attenuated in Iqgap3-cKO mice. We further showed that Iqgap3 directly interacted with Myc, which reinforces a role of Iqgap3 in enhancing Myc activity. Our findings highlight the critical roles of the Iqgap3-Myc axis in the regulation of stem cell activity, gastric tissue regeneration and precancerous metaplasia and dysplasia development. These insights provide a mechanistic framework for understanding the intersection of tissue repair and early carcinogenic processes. Citation Format: Junichi Matsuo, Mitsuhiro Shimura, Jungwon Lee, Linda S. Chuang, Wei Peng Yong, Yoshiaki Ito. Iqgap3 and Myc interaction regulates damaged stomach repair and early gastric carcinogenesis [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 121.
Abstract 685: Integrative screening of DNA methylation markers enables early detection of hepatocellular carcinoma
Authors: Hao Zhuang, Bo Wang, Yongmei Li
Journal: Cancer Research (2025)

Abstract DNA methylation, a pivotal epigenetic modification regulating gene expression, has gained significant attention as a potential diagnostic biomarker for various cancers, including hepatocellular carcinoma (HCC). This study aimed to identify aberrant DNA methylation patterns and protein alterations using integrated methodologies and to develop a robust biomarker panel for blood-based early detection of HCC. Genome-wide methylation profiling was performed to identify hypermethylated CpG sites and genes that distinguish early-stage HCC from non-HCC tissues. Using four distinct strategies, 44 candidate marker genes were identified and subsequently assessed in combination with five protein markers in a cohort of 299 blood samples. Through 5-fold cross-validation, a panel comprising six methylation markers from four different groups achieved an area under the curve (AUC) of 0.938, outperforming panels derived from single-group markers. A final 6-marker panel, combining four methylation markers and two protein markers in a logistic regression (LR) model, was developed. This panel demonstrated a sensitivity of 92.2% at a specificity of 94.3% in the training set, and a sensitivity of 86.4% at a specificity of 97.8% in the validation set. Notably, the 6-marker panel showed superior sensitivity (75.0%) for detecting HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0-A compared to alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP). A multi-group approach to selecting methylation markers outperformed single-group strategies. The developed 6-marker panel demonstrates excellent sensitivity and specificity, offering a promising tool for the early detection of HCC, particularly in its earliest stages. Citation Format: Hao Zhuang, Bo Wang, Yongmei Li. Integrative screening of DNA methylation markers enables early detection of hepatocellular carcinoma [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 685.
Abstract 850: Development of a systemic enveloped immunovirotherapy for targeting metastatic sites
Authors: Yunyi Kang, Duong Nguyen, Trevor Smith, Stephanie Songco, Forrest Neuharth, Ivelina Minev, Karolin Streule, Selamawit Alemu, Lina Schulte, Thomas Herrmann, Boris Minev, Antonio Santidrian
Journal: Cancer Research (2025)

Abstract Background: Systemic virotherapies targeting directly all tumors are a promising form of cancer immunotherapy not only due to their tumor lytic characteristics but also because of their potential to transform tumor immune microenvironment, and targeted delivery of virus-encoded therapeutic payloads into tumors. Developing a platform for systemic delivery would provide a significant advantage in treating both primary tumors and any metastatic lesions. However, systemic administration of virotherapies may pose challenges of increased toxicity and reduced efficacy due to rapid virus clearance. In order to overcome these limitations, we have selected and developed a novel enveloped vaccinia virus platform by isolating a complement-resistant strain called Redtail vaccinia virus (RT). We have further engineered the backbone of the isolated strain to achieve tumor specific targeting and high therapeutic efficacy. Methods: The RT backbone was genetically engineered by deleting multiple metabolic and immuno-modulatory genes. The replications of lead RT candidates were compared in vitro by xCELLigence real time cell analysis. In addition, therapeutic efficacy and toxicity profile of the candidate RT were monitored through in vivo imaging and clinical observation in both immunocompromised and immunocompetent mouse models. Results: The newly developed and engineered RT demonstrated significant production of enveloped viruses with improved safety profile and enhanced therapeutic efficacy in metastatic lung cancer mouse models. In the immunodeficient nude mouse model, selected RT modification showed tumor specific targeting and preferential amplification in the tumors. In immunocompetent mouse model, RT lead candidate exhibited significant survival in circulations, tumor targeting, regression of primary and metastatic tumors with acceptable safety profile. In addition, drastic changes in tumor microenvironment were observed. Enveloped RT oncolytic immunotherapy increased cytotoxic T cell infiltration and decreased Tregs at the tumor sites, along with the release of proinflammatory cytokine, ultimately leading to tumor regression. Conclusions: In summary, we have successfully developed a novel enveloped antitumor virotherepy that could be systemically delivered as a form of cancer immunotherapy in a safe manner. Citation Format: Yunyi Kang, Duong Nguyen, Trevor Smith, Stephanie Songco, Forrest Neuharth, Ivelina Minev, Karolin Streule, Selamawit Alemu, Lina Schulte, Thomas Herrmann, Boris Minev, Antonio Santidrian. Development of a systemic enveloped immunovirotherapy for targeting metastatic sites [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 850.
Abstract 459: Discovery and proteomic characterization of a novel KAT6A/B inhibitor
Authors: Gali Arad, Avital Hay-Koren, Sagie Brodsky, Andrew Morley, Iris Alchanati, Galina Otonin, Yonatan Katzenelenbogen, Barr Tivon, Alon Shtrikman, Dimitri Kovalerchik, Anjana Shenoy, Katharina Lange, Nitzan Simchi, Eran Seger, Kirill Pevzner
Journal: Cancer Research (2025)

Abstract Lysine histone acetyltransferase 6 (KAT6A/B) is a MYST family member of histone acetyltransferases (HATs), known to regulate gene expression by acetylation of both histone and non-histone substrates. KAT6A/B is a promising cancer drug target, specifically in estrogen receptor positive (ER+) breast cancer, but anti-cancer activity in other cancer indications has also been shown, suggesting a potential benefit for wider patient populations. Despite antitumor activity observed in clinical trials, KAT6i inhibitors are also reported to cause several high grade adverse events, including dysgeusia, neutropenia, and anemia, in some cases leading to treatment discontinuation. The efficacy alongside tolerability profiles of KAT6i reflects the need for improved therapeutic window by developing cleaner, more selective drugs; as well as by identification of additional responsive populations. By applying computational and medicinal chemistry approaches we discovered a novel, highly potent inhibitor of KAT6A/B, demonstrating anti-tumor activity using both in-vitro cell viability assays and tumor growth inhibition in xenograft models. We combined drug sensitivity with basal and perturbational proteomics data of cancer cell lines, in order to provide a mechanistic explanation of KAT6A/Bi mode of action. Proteomic analysis of KAT6i sensitive and resistant cell lines highlighted several candidates for KAT6 predictive biomarker and shed light on the proteome-wide effects of KAT6 inhibition. In summary, these results support KAT6i drug development both within and outside ER+ breast cancer, as well as optimization of more selective KAT6 inhibitors to improve tolerability and therapeutic window. Citation Format: Gali Arad, Avital Hay-Koren, Sagie Brodsky, Andrew Morley, Iris Alchanati, Galina Otonin, Yonatan Katzenelenbogen, Barr Tivon, Alon Shtrikman, Dimitri Kovalerchik, Anjana Shenoy, Katharina Lange, Nitzan Simchi, Eran Seger, Kirill Pevzner. Discovery and proteomic characterization of a novel KAT6A/B inhibitor [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 459.
Abstract 28: Novel organoid-based exploration reveals the role of LMTK3/FADS2 signaling in metastatic breast cancer progression in cats and humans
Authors: Haru Yamamoto, Mohamed Elbadawy, Tatsuya Usui, Kazuaki Sasaki
Journal: Cancer Research (2025)

Abstract Cat breast cancer (CBC) is the third most common type of feline neoplasm. It constitutes approximately 17% of feline tumors, with an estimated annual incidence of between 13 and 25/100, 000 cats. CBC shares similar histology, genetics, behavior, and clinicopathological characteristics with human BC. Despite advancements in human breast cancer (BC) treatment, outcomes in human and veterinary medicine remain suboptimal. Spontaneously developed BC in CBC is highly malignant, intractable, and has the potential to become a valuable translational model for human metastatic BC (HBC). We developed primary CBC organoids and analyzed their morphology, gene expression patterns, and response to anti-cancer drugs. CBC organoids recapitulated the structure and behavior of tumor cells, exhibiting diverse hormone receptor expressions and tumorigenic potential. Moreover, varying sensitivities to chemotherapies and targeted drugs were evident across CBC organoid lines. Furthermore, LMTK3 was significantly upregulated in CBC organoids compared to normal organoids. Further, LMTK3/FADS2 pathway was revealed to be implicated in progression and metastasis by influencing cell proliferation, invasion, and apoptosis of CBC organoids. Cell viability of human BC organoids was also prevented by treatment of LMTK3 inhibitor. Survival time of human BC patients with high co-expression of LMTK3 and FADS2 was shorter than that with low co-expression. These findings highlight the importance of LMTK3/FADS2 pathway in BC progression and indicate that companion animal cancer organoid research can model HBC. Citation Format: Haru Yamamoto, Mohamed Elbadawy, Tatsuya Usui, Kazuaki Sasaki. Novel organoid-based exploration reveals the role of LMTK3/FADS2 signaling in metastatic breast cancer progression in cats and humans [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 28.