tbuckley/cabot-search huggingface dataset:
Abstract 5726: QLS1103, A highly potent and selective PARP7 inhibitor treating advanced solid tumors
Authors: Yuxing Zhang, Xiaoxia Yan, Yiming Xu, Difei Dong, Huijie Guo, Junguo Hao, Xinrui Shao, Ling Li, Guanxin Huang, Dong Yang, Guqin Shi, Yanling Xu, Daqing Sun, Weimei Sun, Weikang Tao
Journal: Cancer Research (2025)

PARP7, a member of the ADP-ribose polymerase family, is an enzyme that modifies proteins by attaching mono ADP-ribose to substrates. This post-translational modification is crucial for a variety of cellular functions, including the regulation of innate immune responses, the control of autophagy, and the facilitation of apoptosis. In some tumor cells, PARP7 may facilitate immune surveillance evasion by inhibiting type I interferon signaling pathways. Additionally, PARP7 has been reported to promote tumor growth in a cell-autonomous manner. Due to its multifaceted functions, PARP7 is an important target for cancer research and therapeutic intervention. QLS1103 is a proprietary, highly potent and selective PARP7 inhibitor. Study findings showed that treatment with QLS1103 may restore Type I IFN responses in tumor cells and trigger anti-tumor immunity in CT26 and EO771 syngeneic models. Analysis of tumor-infiltrating lymphocytes (TILs) revealed that QLS1103 not only increases the percentage of TILs but also enhances the activity of cytotoxic T cells. Furthermore, the combination of QLS1103 with an anti-PD-1 antibody showed a significant survival benefit over monotherapy in the CT26 model, with a complete regression (CR) rate rising to 75% in the combination group, compared to 25% in the monotherapy group. QLS1103 was also evaluated in a lung cancer xenograft model (NCI-H1373) to confirm the cell-autonomous effects of PARP7 inhibition. It was observed that QLS1103 could dose-dependently inhibit tumor growth and even induce tumor regression. QLS1103 has exhibited a favorable safety profile with excellent safety margins in preclinical studies and is currently under investigation in a phase I clinical trial. In conclusion, QLS1103 emerges as a promising candidate for the treatment of advanced solid tumors, either as a monotherapy or in combination with immune checkpoint inhibitors, warranting further investigation in clinical settings to fully realize its therapeutic potential. Citation Format: Yuxing Zhang, Xiaoxia Yan, Yiming Xu, Difei Dong, Huijie Guo, Junguo Hao, Xinrui Shao, Ling Li, Guanxin Huang, Dong Yang, Guqin Shi, Yanling Xu, Daqing Sun, Weimei Sun, Weikang Tao. QLS1103, A highly potent and selective PARP7 inhibitor treating 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 5726.
Abstract 3690: Biomarker Navigator - empowering the augmented scientist in biomarker discovery
Authors: Ioannis Kagiampakis, Mishka Gidwani, Iaroslav Korkodinov, Georgiy Ponomarev, Sun Gerald, Etai Jacob, Damian Bikiel
Journal: Cancer Research (2025)

Abstract The advent of large language models (LLMs) is poised to revolutionize every domain of the pharmaceutical industry, from early-stage drug development to clinical trial design. By harnessing both public datasets and scientific literature, LLMs offer unparalleled access to critical knowledge for researchers, while proprietary datasets provide a unique competitive edge, enabling organizations to derive exclusive insights and drive innovation. To excel in biomarker development within large organizations, two critical goals must be prioritized: maximizing the extraction of insights from proprietary datasets and ensuring the seamless dissemination of knowledge across the organization. Large Language Models (LLMs) facilitate these goals by connecting expertise across diverse scientific domains and delivering knowledge in natural language. This enables the creation of an “augmented scientist” empowered to make data-driven decisions and generate hypotheses through the integration of cross-disciplinary knowledge. The Biomarker Navigator program exemplifies AstraZeneca’s commitment to this augmented scientist vision through three core components: 1) an automated analysis framework for biomarker identification. 2) a comprehensive repository of standardized, detailed biomarkers insights. 3) an intuitive interface for fast, seamless knowledge access. AstraZeneca is expanding the Biomarker Navigator by integrating public datasets to make it accessible to the broader scientific community, with an initial focus on renal cell carcinoma (RCC) and melanoma. This dataset expansion includes whole exome sequencing (WES), copy number alterations (CNA), RNA sequencing (RNA-seq), and clinical metadata. The resulting system empowers researchers to seamlessly transition from a high-level overview of the biomarker landscape—within or across datasets—to detailed insights about a single biomarker, ensuring no information is lost. By combining an intuitive user interface with LLM-driven insights, this platform showcases the transformative potential of AI in biomarker discovery, paving the way for a robust, open-source framework for the scientific community in the near future. Citation Format: Ioannis Kagiampakis, Mishka Gidwani, Iaroslav Korkodinov, Georgiy Ponomarev, Sun Gerald, Etai Jacob, Damian Bikiel. Biomarker Navigator - empowering the augmented scientist in biomarker discovery [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 3690.
Abstract 3719: Docking analyses of miR-21 with RNA-binding proteins that interact with BRCA1
Authors: Yelyzaveta Khayman, Shaneen Singh, Anjana Saxena
Journal: Cancer Research (2025)

Abstract RNA binding proteins (RBPs) are key post-transcriptional regulators that predominantly control gene expression through RNA metabolism. Dysregulation of RBPs is implicated in therapy resistance of breast cancer and targeting key RBPs can be a promising therapeutic approach to reverse this resistance. However, the RBP-related mechanisms in breast cancer are complex, influencing the critical proteins involved in cellular DNA damage response (DDR) at one end and modulating the processing of primary miRNA (pri-miRNA) structures to precursor forms on the other end. Studies strongly demonstrated that a stress-responsive RBP, namely nucleolin (NCL) co-localizes with the tumor suppressor breast and ovarian cancer susceptibility gene (BRCA1) during DDR and regulates the expression of a specific subset of miRNAs (miR-21, miR-221, miR-222, and miR-103) that are causally involved in breast cancer initiation, progression, and drug resistance. Earlier we generated docking scenarios with this subset of miRNAs to demonstrate a role of NCL-RNA-binding domain (RBD) 3 and 4 playing a significant role in such interactions. We also identified a group of RBPs as common interactors of BRCA1 and NCL, namely heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1), heterogeneous nuclear ribonucleoprotein D (HNRNPD), polyadenylate binding protein cytoplasmic 1(PABPC1), and TAR DNA-binding protein 43 (TDP-43). Interestingly, miR-21 is revealed as a known predicted target of this subset of RBPs. In this study, we therefore focus on modeling docking scenarios of miR-21 with these four RBPs and assessed NCL-binding to miR-21. In this study, we utilized complete RBD regions of these RBPs to predict models for RBP-miR-21 interactions, to highlight the conserved motifs participating in such an interaction. Next, we propose models of competitive versus synergistic binding of miR-21 with the different RBPs. The computational models generated in this study will provide key insights about the RBP- miR-21 interacting interfaces. Additionally, RBP-BRCA1 collaborations further provides insights about how miR-21 regulation by RBP play a role in defective DNA repair mechanism in breast cancer that could serve as potential for therapeutic intervention. Citation Format: Yelyzaveta Khayman, Shaneen Singh, Anjana Saxena. Docking analyses of miR-21 with RNA-binding proteins that interact with BRCA1 [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 3719.
Abstract 3675: An integrated approach for simultaneous detection of genomic and epigenetic alterations in blood-based ctDNA analysis
Authors: Qin Tang, Becky Wong, Varahenage Namali Perera, Yu Sun, Nafisa Bulsara, Brian Giacopelli, James Yu, Jason Close, Peter George, Andy Eang, Ashley Linares, Andrew S. Lee, Neil Peterman, Alex Robertson, Nicole Lambert, Yexun Wang
Journal: Cancer Research (2025)

Abstract Cancer harbors abnormalities in the genome and the epigenome, and both can serve as biomarkers to facilitate its detection. We developed an integrated multi-omic approach to identify genomic and methylation alterations simultaneously from blood-based circulating tumor DNA (ctDNA) analysis. In contrast to traditional methods of separated lab workflows for each signal modality, our lab workflow generates both genomic and methylation sequencing libraries from the same input sample. During the workflow, a cytosine conversion-resistant analog of the original cell-free DNA (cfDNA) molecule is synthesized such that its genomic sequence is preserved. Following cytosine conversion of the original cfDNA and its analog in a single reaction, methylation and genomic libraries are respectively derived. A new signal modality identification design is used for separation of genomic and methylation libraries during data processing. Our strategy has the benefit of reducing operational complexity while maximizing ctDNA capture efficiency from small quantities of analyte. Our results show that the multi-omic library is efficiently synthesized (52.8% of genomic reads and 47.2% methylation reads after parsing signal modality identifier), and that the genomic library is effectively protected from cytosine conversion (99.98% protection efficiency). Filtered conversion efficiency exceeds 99.9% in CH (where H corresponds to A, T or C) context from the methylation library, supporting high signal integrity in the methylation workflow. Genomic variant calling detected known cancer variants in FFPE tissue and plasma samples (&amp;gt;96% variants in FFPE tissue samples from stage II and III cancers). In a small clinical cohort study, the methylation signal modality detected 40% of stage I, 95% of stage II and 87% of stage III lung cancer plasma samples at 100% specificity without requiring matching tissue. Taken together, our integrated multi-omic approach provides a versatile tool for combined sensitivity and actionability in blood-based ctDNA detection. Citation Format: Qin Tang, Becky Wong, Varahenage Namali Perera, Yu Sun, Nafisa Bulsara, Brian Giacopelli, James Yu, Jason Close, Peter George, Andy Eang, Ashley Linares, Andrew S. Lee, Neil Peterman, Alex Robertson, Nicole Lambert, Yexun Wang. An integrated approach for simultaneous detection of genomic and epigenetic alterations in blood-based ctDNA analysis [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 3675.
Abstract 5738: Napabucasin analogues with increased bioavailability and efficacy in fibrolamellar hepatocellular carcinoma
Authors: Shalini Rawat, Jared Alderman, Priscilla Baeza, Lianna Hartshorn, Celeste Villasenor, Jakim Brazil, Barbara Lyons
Journal: Cancer Research (2025)

Fibrolamellar Hepatocellular carcinoma (FLC) is a very rare liver cancer which occurs in young adults and children under the age of 40. This cancer is lethal and was first recognized in 1980. The term “fibrolamellar” refers to the fibrous bands that are visible when examining tumor tissue under a microscope. In FLC, a deletion of 400,000 base pairs occurs in a chromosome 19 copy, leading to the formation of a fusion protein comprising heat shock protein DNAJB1 and the catalytic subunit of Protein Kinase A (DNAJB1-PRKACA). Patients show no symptoms in the early stage of the disease. The reported survival rate over the past five years is below 50%. Surgery remains the sole partially effective treatment for FLC, with no currently approved systemic therapies available. The primary model compound of this project is Napabucasin. It is also known as BBI608 is a naphthoquinone natural product isolated from the plants Newbouldia laevis, Ekmanianthe longiflora, and Handroanthus impetiginosus. It has shown wide spectrum anti-cancer activities and is now in trials for cancer treatment. The Napabucasin was found to be a top hit in drug screening showing potency against all FLC patient derived xenografts (PDX) models. Napabucasin is known to work in multiple signaling pathways and have been shown cytotoxic against both PDX and direct-from-patient FLC tumor cells. We anticipate that the organic synthesis and development of optimized Napabucasin analogues, along with the evaluation of their cytotoxicity and proliferation effectiveness compared to the parent compound, Napabucasin, will result in compounds with improved bioavailability and efficacy, particularly in FLC model cell lines (FLX1 and Huh7-Chimera). Citation Format: Shalini Rawat, Jared Alderman, Priscilla Baeza, Lianna Hartshorn, Celeste Villasenor, Jakim Brazil, Barbara Lyons. Napabucasin analogues with increased bioavailability and efficacy in fibrolamellar 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 5738.
Abstract 4132: PTPRF negatively regulates c-MET signaling to inhibit cell migration in colon cancer
Authors: Carolina Galeano-Naranjo, Haley Stanczyk, Warren Van Nort, Tianyan Gao
Journal: Cancer Research (2025)

Abstract The spatiotemporal control of cell signaling requires a balancing act of protein kinases and phosphatases. Hyperactivation of signaling downstream of receptor tyrosine kinases (RTKs) is one of the most common mechanisms leading to oncogenic transformation in numerous cancer types. Although the activation process of RTKs has been extensively studied, the inactivation mechanisms mediated by tyrosine phosphatase are less understood. Previously, we have determined the molecular mechanisms by which protein tyrosine phosphatase receptor type F (PTPRF) regulates the Wnt pathway. In this study, we investigated the functional importance of PTPRF in controlling c-MET signaling in colon cancer. Downregulation of PTPRF in colon cancer cells using CRISPR-mediated gene deletion or shRNA-mediated gene silencing activates c-MET signaling at the level of GAB1 scaffolding protein upon HGF-induced receptor activation. Co-immunoprecipitation experiments indicate that PTPRF interacts with the c-MET receptor/GAB1 complex. In addition, PTPRF downregulation prolongs the phosphorylation of GAB1 in colon cancer cells treated with c-MET inhibitor. Functionally, PTPRF-loss markedly increases cell migration. Moreover, bioinformatics analysis of TCGA colon cancer patient data reveals that the expression of PTPRF gene is significantly decreased in tumor samples compared to normal controls. Taken together, these results identify PTPRF as a novel phosphatase of GAB1 that negatively regulates c-MET signaling. Decreased expression of PTPRF may play an important role in promoting tumor progression in colon cancer. Citation Format: Carolina Galeano-Naranjo, Haley Stanczyk, Warren Van Nort, Tianyan Gao. PTPRF negatively regulates c-MET signaling to inhibit cell migration in colon 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 4132.
Insulin Autoimmune Syndrome
Authors: Rucha Barapatre, Priyanka Verma, Anurag R. Lila, Sandip Basu
Journal: Clinical Nuclear Medicine (2025)

A 62-year-old woman who experienced a seizure was found to be hypoglycemic. A prolonged fasting test revealed raised critical insulin and C-peptide levels. CECT of the abdomen demonstrated an isodense focus in the tail of the pancreas. On the suspicion of insulinoma, she was referred for a 68 Ga-Exendin-4 PET/CT study, which revealed diffuse tracer uptake in the entire pancreatic tissue. She also underwent a 68 Ga-DOTATATE PET/CT scan, which demonstrated physiological uptake in the pancreas. She later tested positive for anti-insulin antibodies. We herein report a positive Exendin-4 PET/CT study in a case of insulin autoimmune syndrome with its uptake pattern in this entity.
18F-FDG PET/CT Imaging of Eosinophilic Granulomatosis With Polyangiitis
Authors: Yuyan Chen, Qiaoqiao Shu, Yixuan Li, Maoxue Deng, Liang Cai
Journal: Clinical Nuclear Medicine (2025)

A 29-year-old woman presented with asthma, fever, generalized rash, and numbness in the ring and pinky fingers of her right hand. Laboratory studies showed significant increases in blood eosinophils, C-reactive protein, and IgE, but ANCA (antineutrophil cytoplasmic antibodies) were negative. The 18 F-FDG PET/CT suggests scattered, segmented FDG uptake around small and medium vessels throughout the body. After comprehensive analysis, the patient's final clinical diagnosis was eosinophilic granulomatous vasculitis.
Urethral Diverticulum Mimicking Metastatic Prostate Cancer on 68Ga-PSMA-11 PET/CT
Authors: Xiaojun Man, Changming Dong, Xiandong Song, Aisheng Dong
Journal: Clinical Nuclear Medicine (2025)

Urethral diverticulum rarely occurs in a man. A 57-year-old man who underwent radical prostatectomy for prostate adenocarcinoma 9 years ago was referred for 68 Ga-PSMA-11 PET/CT scan for restating due to elevated serum total prostate-specific antigen level. 68 Ga-PSMA-11 PET/CT showed multiple PSMA-avid bone metastases and a focal intense activity in the anterior penis. The PSMA-avid penil lesion corresponded to a urethral diverticulum, which was initially detected on pelvic MRI 8 years ago. This case indicates that the urethral diverticulum should be included in the differential diagnosis of PSMA-avid penile lesions.
Single-cell analysis of proximal tubular cells with different DNA content reveals functional heterogeneity in the acute kidney injury to chronic kidney disease transition
Authors: Fugang Li, Qigang Lan, Yaqin Wang, Jiachuan Xiong, Tangli Xiao, Shuiqin Gong, Yan Li, Shaobo Wang, Mengying Yao, Liangjing Lv, Shaozong Qin, Wang Xin, Li Liu, Bo Zhang, Jinghong Zhao
Journal: Kidney International (2025)
Abstract 6027: Translational medicine studies of BRY812, an anti-LIV-1 antibody drug conjugate for cancer therapeutics
Authors: Qinqin Zhuang, Qianqian Tao, Xiaobei Zhao, Jie Zhu, Lei Nie, Gang Chen, Haibin Wang
Journal: Cancer Research (2025)

Abstract LIV-1, also known as SLC39A6 or ZIP6, belongs to the zinc transporter family and was initially identified as an estrogen-inducible gene in breast cancer. Immunohistochemical (IHC) analysis have revealed escalated LIV-1 expression in estrogen receptor-positive (ER+), hormone-treated tumors (both primary and metastatic sites) as well as ER-/PR-/Her2- (triple-negative) breast cancers. Notably, healthy human tissues exhibit limited LIV-1 expression, primarily in hormone regulated organs (prostate, uterus, and breast). The escalated expression of LIV-1 in breast and prostate cancer, as well as melanoma and other tumors, positions LIV-1 as an excellent target for ADC therapeutics. BRY812 is a monomethyl auristatin E (MMAE)-conjugated humanized IgG1 ADC against LIV-1. With Bioray’s irreversible conjugation method CysLinkTM, BRY812 enables superior in vivo stability and eliminates off-target payload migration. Recent translational medicine studies have shown that BRY812 exhibits favorable efficacy in in vitro models of Breast cancer and Endometrial cancer. Additionally, BRY812 has demonstrated synergistic efficacy when combined with PD-1/L1 antibodies in a series of in vitro and in vivo models. Finally, BRY812 has shown improved efficacy in DS-8201 resistant cell line compared to the parental cell line. These results showed that BRY812, either as a monotherapy or in combination with other drugs, has a significant potential for application in various solid tumor indications, as well as in patients who are resistant to existing therapies. Citation Format: Qinqin Zhuang, Qianqian Tao, Xiaobei Zhao, Jie Zhu, Lei Nie, Gang Chen, Haibin Wang. Translational medicine studies of BRY812, an anti-LIV-1 antibody drug conjugate for cancer therapeutics [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 6027.
Abstract 6032: Intratumoral Tregs restrain the immune response against primary and metastatic cancer
Authors: Alissa Bockman, Mariela Moreno Ayala, Brenna Gittins, Chenyu Zhang, Skye Benyon, Michel DuPage
Journal: Cancer Research (2025)

Abstract Advancements in cancer immunotherapies have significantly improved patient outcomes in hematologic malignancies but are dramatically limited by the suppressive function of Regulatory T cells (Tregs) in solid cancers. Antibody-based therapeutics, such as anti-CTLA-4 and anti-CCR8, are being tested to selectively deplete intratumoral Tregs, with promising preclinical efficacy. However, these therapies have multiple effects that may do more than just deplete intratumoral Tregs, such as activate Fc receptors, bind to other types of immune cells, or bind to cells outside of the tumor microenvironment. While Tregs highly infiltrate most tumor types, it is unclear whether they function to suppress cancer immunity only in tumor tissue itself or at peripheral sites. To test whether Tregs function directly within the tumor microenvironment to suppress antitumor immune responses, we developed a model in which intratumoral (IT) delivery of low-dose diphtheria toxin (DT) in Foxp3DTR mice is used to only deplete IT Tregs. We show that mice that receive IT DT have reduced Tregs frequencies only in the tumor and do not succumb to lymphoproliferative disease, as observed with systemic Treg depletion. Critically, tumor Treg ablation via IT DT produced more effective and durable tumor control than systemic Treg ablation. Mechanistically, we show that robust tumor control is achieved through enhanced function of effector CD4+ and CD8+ T cells and requires MHC II+ CD11b+ Batf3- type 2 conventional dendritic cells. Through the use of disseminated tumor models, we find that disrupting Treg suppression within a primary tumor unleashes antitumor immunity against metastatic lesions that are not directly treated. Interestingly, this multifocal tumor control is dependent upon the cooperation between CD4+ and CD8+ T cells and requires matched primary and metastatic tumors. Through in vivo cellular trafficking experiments and blockade of T cell egress from lymphoid tissues we show a high frequency of Tregs circulate between local and metastatic tumors to mediate systemic immune effects. Upon disruption of tumor-Treg circulation between lesions, we demonstrate enhanced effector function and decreased disease burden at both tumor sites. These findings identify a tumor-resident Treg niche that limits CD4+-cDC2 mediated antitumor immune responses. Importantly, our results uncover a novel Treg suppressive mechanism that promotes systemic cancer progression. Citation Format: Alissa Bockman, Mariela Moreno Ayala, Brenna Gittins, Chenyu Zhang, Skye Benyon, Michel DuPage. Intratumoral Tregs restrain the immune response against primary and metastatic 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 6032.