tbuckley/cabot-search huggingface dataset:
Abstract 1801: Development and evaluation of KMD111: A HER2-targeted novel drug delivery system for gastric and breast cancer therapy
Authors: Jong Kook Rho, Gyeong Hee Lee, Seung Min Byun, Hyo Kyoung Park, JinBeam Kim, YoungKuk Yun, Myung Hoon Kim
Journal: Cancer Research (2025)

Abstract Background: HER2-low expressing cancers, including gastric and breast cancers, have historically been categorized as HER2-negative, limiting targeted therapy options. To address this, we developed KMD111, a novel HER2-targeted drug delivery platform using mesoporous silica nanoparticles (MSNs) loaded with a potent anticancer drug and coated with HER2-targeting affibody proteins via a glutathione-sensitive GST-GSH bio-linker. KMD111 demonstrated high tumor-targeting efficiency, superior anti-tumor efficacy, and a favorable safety profile in preclinical models, providing stability in the bloodstream and selective drug release regulated by GSH concentrations in the tumor microenvironment. Methods: KMD111 was synthesized by conjugating HER2-targeting affibody proteins to drug-loaded MSNs. Binding affinity and internalization were assessed in HER2-expressing cancer cell models. Anti-tumor efficacy was evaluated in gastric and breast cancer xenografts, while mechanistic studies examined cell cycle arrest, apoptosis activation, and HER2 signaling inhibition. Safety was evaluated through macrophage uptake, histopathological analysis, and toxicity testing. Results: KMD111 demonstrated efficient drug loading and GSH-responsive drug release in vitro, with high tumor-targeting efficiency and strong internalization in HER2-expressing cancer cells. It exhibited superior anti-tumor efficacy compared to Enhertu®, Kadcyla®, and Cyramza® and effectively triggered cell cycle arrest and apoptosis activation through a potent anticancer drug. KMD111 also showed a favorable safety profile, including minimal macrophage uptake, negligible myelosuppression, and no significant off-target toxicity, with a therapeutic index exceeding five times the effective dose. Conclusion: KMD111 demonstrates robust targeting, high therapeutic efficacy, and a favorable safety profile in HER2-expressing gastric and breast cancer models. This innovative approach, leveraging a glutathione-regulated bio-linker for enhanced delivery and tumor specificity, represents a promising foundation for next-generation drug delivery systems targeting HER2-expressing malignancies. Citation Format: Jong Kook Rho, Gyeong Hee Lee, Seung Min Byun, Hyo Kyoung Park, JinBeam Kim, YoungKuk Yun, Myung Hoon Kim. Development and evaluation of KMD111: A HER2-targeted novel drug delivery system for gastric and breast cancer 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 1801.
Abstract 3156: A surface plasmon resonance-based screening platform to identify potential PD-1/PD-L1 inhibitors from a FDA-approved drugs library for cancer immunotherapy
Authors: Huifang Li, Ang Cai, Navindra P. Seeram, Chang Liu
Journal: Cancer Research (2025)

Abstract The PD-1/PD-L1 axis plays a pivotal role in immune checkpoint regulation in cancer, making its inhibition a key strategy in cancer immunotherapy. However, the development of small molecule inhibitors targeting PD-1/PD-L1 interaction has been hindered by the lack of robust high-throughput screening platforms. In this study, we developed a high-throughput screening platform based on surface plasmon resonance (SPR) technology, utilizing a 384-well plate format. This platform integrates a dual-step coupling method, employing both amine and bio-streptavidin coupling to optimize PD-1 orientation on the sensor chip.We screened a library of 2, 764 FDA-approved drugs using this SPR platform with a 1:1 ratio of drug to PD-L1, alongside two positive control PD-L1 inhibitors. Three compounds, RB, MB, and VP, were identified as hits, showing PD-1/PD-L1 blockade rates of 13.1%, 9.6%, and 6.7%, respectively, compared to the positive controls BMS-1166 (33%) and BMS-202 (8.4%). Structural validation through saturation transfer difference nuclear magnetic resonance (STD-NMR) spectroscopy confirmed the binding of RB to PD-L1, with a unique STD peak at 7.6 ppm, further supported by a WaterLOGSY control experiment indicating a negative nuclear overhauser effect to water. The dissociation constants KD of RB were determined using SPR, revealing moderate binding affinities to PD-L1.Cytotoxicity assays conducted on Jurkat T cells and A375 melanoma cells demonstrated that RB exhibited no toxicity across a concentration range from 100 μM to 0.01 μM. Functional assays using a co-culture model of T cells and cancer cells, designed to replicate the tumor microenvironment, showed that RB treatment modulated IL-2 secretion and induced apoptosis in A375 cancer cells. Proteomic analysis of sorted Jurkat T cells from the co-culture model via bottom-up proteomics revealed key proteins and signaling pathways regulated by RB.Overall, these findings suggest that RB exerts significant PD-1/PD-L1 inhibitory activity and may hold promise as a repurposed drug candidate for cancer immunotherapy. Citation Format: Huifang Li, Ang Cai, Navindra P. Seeram, Chang Liu. A surface plasmon resonance-based screening platform to identify potential PD-1/PD-L1 inhibitors from a FDA-approved drugs library 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 3156.
Abstract 6189: Educational level as a determinant of breast cancer stage at diagnosis
Authors: Xiaying Kuang
Journal: Cancer Research (2025)

Abstract Background: Presently, there is a gap in literature regarding specific demographic characteristics and the stage of breast cancer at diagnosis. Herein, we examined patients' educational levels to explore effective strategies for early breast cancer diagnosis. Methods: Convenience sampling method was used to select invasive breast cancer patients treated at a tertiary hospital in Guangzhou between January 2018 and March 2023 to determine patients' breast cancer stage at diagnosis and individual characteristics. The associations were analyzed using Student's t-test and the chi-square test, and binary logistic regression analysis was conducted to assess the odds ratios (ORs) for the occurrence of late-stage breast cancer. Results: The study encompassed a total of 3225 patients diagnosed with invasive breast cancer. Among them, 707 patients were identified with late-stage cancer (stage III-IV), comprising 21.9% of the total sample. Univariate analysis revealed a significant inverse correlation between patients' educational level and the stage of breast cancer at diagnosis, regardless of age stratification. The results of the chi-square test revealed a significant correlation between patients' educational level and their perception of illness (P &amp;lt; 0.001), with patients with higher levels of education being more likely to demonstrate a more comprehensive understanding of the disease. Upon controlling for other potential confounding variables, these findings were confirmed by binary logistic regression analysis, which demonstrated that individuals with lower education levels had a significantly increased likelihood of being diagnosed with late-stage breast cancer (adjusted OR = 1.409 for the middle school group and 1.518 for the illiterate and primary school group). Conclusions: Patients with lower educational levels could be more likely to present with late-stage breast cancer at diagnosis. Therefore, it is imperative to prioritize popular science and early prevention strategies for breast cancer among less educated populations. Citation Format: Xiaying Kuang. Educational level as a determinant of breast cancer stage at diagnosis [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 6189.
Abstract 6190: Descriptive analysis of selenium levels in a healthy Malawian subpopulation: Findings from a control study on esophageal squamous cell carcinoma (ESCC)
Authors: Emmanuel Uduh, Yukiko Yano, Yingxi Chen, Christian Abnet, Bongani Kaimila, Shiraz Khan
Journal: Cancer Research (2025)

Background: Esophageal squamous cell carcinoma (ESCC) is the third most common cancer in Malawi, with an estimated 1,871 new cases and 1,766 deaths in 2024 in Malawi. Although drinking alcohol and smoking tobacco are major causes of ESCC in some populations, the high rates in Malawi are unlikely to be due to these agents. Several East African countries have high incidence rates of ESCC and low soil selenium concentrations. Observational and intervention studies in East Asia have shown that low selenium concentrations are linked to an increased risk of ESCC. Methods: We used control subjects from a previously reported hospital-based case-control study of ESCC conducted at two hospitals in Lilongwe, Malawi (2017-2020). The study collected questionnaire data and stored fractionated blood. ESCC cases were excluded due to reverse causation for nutritional biomarkers. Instrumental neutron activation analysis (INAA) was used to measure serum selenium concentrations. Using R, we generated descriptive statistics and tested for associations with demographic variables. We also compared this study population to other previously studied populations with high ESCC incidence rates. Results: We successfully measured 247 control subjects from Malawi and found a median (IQR) serum selenium concentration of 77.3μg/L (65.9-89.5). 79 (31.9%) subjects were below the 72.2 subjects μg/L threshold of the median level of selenium We found no statistically significant associations between serum selenium concentrations and demographic characteristics including sex, education, marital status, and several risk factors for ESCC previously identified in the underlying case-control study. The serum selenium concentrations in these subjects were low and similar to previously studied regions where ESCC is common including both Bomet, Kenya and Linxian, China. Conclusion: We found low median serum selenium levels in control subjects from a hospital-based case-control study of ESCC conducted in Malawi, a region known to have high rates of ESCC. The range was similar to other populations with high incidence of ESCC. Direct linkage to disease risk will require different study designs, but our findings suggest that selenium deficiency could be a factor in the high burden of ESCC in East Africa. Citation Format: Emmanuel Uduh, Yukiko Yano, Yingxi Chen, Christian Abnet, Bongani Kaimila, Shiraz Khan. Descriptive analysis of selenium levels in a healthy Malawian subpopulation: Findings from a control study on esophageal squamous cell carcinoma (ESCC) [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 6190.
Abstract 6010: Evaluation of BsABN501: A novel T cell engager targeting CLDN3-positive solid tumors
Authors: Saehyung Lee, Sangin Lee, Sunghyun Hong, Jaemun Kim, Jae Choi, Hobin Yang, Sungyoul Hong, Na Young Kim, Jun Young Choi, Young Kee Shin
Journal: Cancer Research (2025)

Claudin 3 (CLDN3) plays a critical role in tumor initiation, progression, and metastasis and is overexpressed in multiple solid tumors, including breast, ovarian, and small cell lung cancers. Previously, ABN501 was developed as a fully human monoclonal antibody targeting CLDN3, demonstrating strong anti-tumor activity and a favorable safety profile. In this study, we established the proof of concept for BsABN501, a CD3 T cell engager, utilizing the anti-CLDN3 sequence derived from the novel antibody ABN501. BsABN501 specifically binds to CLDN3 while concurrently targeting CD3 on T cells, thereby initiating T cell-mediated cytotoxicity (TDCC) against tumor cells. In vitro assays demonstrated that BsABN501 effectively activates peripheral blood mononuclear cells, resulting in potent TDCC against CLDN3-positive cancer cell lines. Notably, BsABN501 exhibited robust cytotoxic activity against CLDN3-expressing tumor cell lines compared to controls. Cytokine release assays further confirmed tumor-specific activation of T cells. Additionally, in vivo studies using xenograft mouse models bearing CLDN3-expressing tumors showed that BsABN501 induced significant tumor regression, highlighting its robust anti-tumor activity. In summary, BsABN501 represents a novel and promising therapeutic strategy for the treatment of CLDN3-positivie solid tumors by effectively recruiting and activating T cells to enhance TDCC. Moving forward, we aim to optimize the CD3 sequence and format of BsABN501 to further improve its anti-cancer efficacy and safety, paving the way for its development as a targeted immunotherapeutic for CLDN3-expressing malignancies. Citation Format: Saehyung Lee, Sangin Lee, Sunghyun Hong, Jaemun Kim, Jae Choi, Hobin Yang, Sungyoul Hong, Na Young Kim, Jun Young Choi, Young Kee Shin. Evaluation of BsABN501: A novel T cell engager targeting CLDN3-positive 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 6010.
Abstract 3163: Discovery of highly selective ligands for the Bcl-2 family of proteins using DNA-encoded chemical libraries
Authors: Ying Zhang, Sana Bazzaz, Corey Bienstock, Paolo A. Centrella, Marie-Aude Guié, John P. Guilinger, Anthony D. Keefe, Matthew A. Clark
Journal: Cancer Research (2025)

DNA-encoded chemical library (DEL) technology enables the efficient screening of large collections of encoded compounds and has emerged as a powerful tool for hit identification. De Novo design and synthesis of non-traditional encoded libraries such as a reversible covalent compound library and beyond Lipinski’s rule of five (bRo5) macrocyclic (MC) libraries have significantly expanded the chemical space available for DEL screening, and further enhances the feasibility of discovering highly selective ligands for challenging oncology targets. We will present examples of affinity-based ligand discovery targeting protein-protein interactions within the Bcl-2 family of proteins, specifically focusing on MCL1 and BFL1. We highlight the multiplexed DEL selection strategy employed and elucidate the molecular details around the uniqueness of the ligand interactions. Citation Format: Ying Zhang, Sana Bazzaz, Corey Bienstock, Paolo A. Centrella, Marie-Aude Guié, John P. Guilinger, Anthony D. Keefe, Matthew A. Clark. Discovery of highly selective ligands for the Bcl-2 family of proteins using DNA-encoded chemical libraries [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 3163.
Abstract 3662: DNA-encoded chemical library screening and machine-learning for hit identification for WD40 repeat targets including oncology targets such as DCAF1, WDR5 and WDR12
Authors: Anthony D. Keefe, Arrash J. Baghaie, Paolo A. Centrella, Matthew A. Clark, Marie-Aude Guié, John P. Guilinger, Jenny Liu, Ryan T. Walsh, Ying Zhang
Journal: Cancer Research (2025)

Abstract Training machine-learned models using DNA-Encoded Chemical Library screening data “DEL-ML” and using these models to rank compounds in virtual catalogs has been successful for hit identification for a range of individual oncology targets including ER alpha and c-KIT [McCloskey et al 2020]. Here we describe the importance of library quality and diversity, protein quality, screen design, appropriate profile choice, training set preparation and evaluation, promiscuity labeling, chemical representations, modeling algorithms and their tuning in the context of a systematic target class-based evaluation for a range of oncology targets including DCAF1, WDR5 and WDR12. This approach yielded first-in-class, drug-like ligands for multiple targets that were characterized using a range of biophysical approaches including x-ray crystallography. Citation Format: Anthony D. Keefe, Arrash J. Baghaie, Paolo A. Centrella, Matthew A. Clark, Marie-Aude Guié, John P. Guilinger, Jenny Liu, Ryan T. Walsh, Ying Zhang. DNA-encoded chemical library screening and machine-learning for hit identification for WD40 repeat targets including oncology targets such as DCAF1, WDR5 and WDR12 [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 3662.
Abstract 5995: Leveraging GPCR overexpression for personalized nanomedicine: A novel approach in ovarian cancer therapy
Authors: Riya Khetan, Preethi Eldi, Noor Lokman, Carmela Ricciardelli, Martin Oehler, Anton Blencowe, Katherine Pillman, Sanjay Garg, Hugo Albrecht
Journal: Cancer Research (2025)

Background and Aims: Genetic heterogeneity in ovarian cancer drives frequent aberrant expression of cell surface proteins including G-protein coupled receptors (GPCRs), which harbour untapped potential for active targeting with nanomedicines. Our goal was to systematically identify GPCRs with significant overexpression in ovarian cancer biopsies and assessing their suitability to develop personalized GPCR-targeted nanomedicines for precise drug delivery. Methods: We ran a systematic analysis of public RNA-seq gene expression data, to reveal GPCRs with frequent overexpression in ovarian cancer tissues. To validate the relevance of initially identified receptors as targeting candidates, we confirmed their expression in six ovarian cancer cell lines and a selection of patient-derived samples (ascites derived tumour samples and solid tumours), using techniques such as RT-qPCR, flow cytometry, fluorescence imaging and immunofluorescence. This comprehensive analysis provided valuable insights into the prevalence and distribution of candidate receptors across different ovarian cancer probes. Furthermore, we utilized representative ovarian cancer cell lines as in vitro models to assess receptor-mediated cellular uptake and internalization processes, to further evaluate potential targets for nanoparticle delivery systems. Results: Analysis of public RNA-Seq datasets revealed 13 overexpressed GPCRs in cancer tissues compared to healthy tissues. Among these, we focused specifically on the coagulation factor II thrombin receptor (F2R) to highlight its intriguing potential as a therapeutic target. The variable expression of F2R was confirmed in both ovarian cancer cell lines and patient-derived samples. Furthermore, peptide binding to the receptor was successfully demonstrated using flow cytometry and fluorescent imaging, suggesting a promising approach for targeted drug delivery. Conclusions and Significance: Our findings underscore the importance of personalized targeting approaches in ovarian cancer therapy and highlight the potential of F2R as a promising therapeutic target. By integrating advanced molecular techniques with nanomedicine strategies, we strive to pave the way for more effective and tailored treatments for ovarian cancer patients. Citation Format: Riya Khetan, Preethi Eldi, Noor Lokman, Carmela Ricciardelli, Martin Oehler, Anton Blencowe, Katherine Pillman, Sanjay Garg, Hugo Albrecht. Leveraging GPCR overexpression for personalized nanomedicine: A novel approach in ovarian cancer 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 5995.
Abstract 2313: Trends in use of neoadjuvant systemic therapy for head and neck squamous cell carcinoma
Authors: Wesley L. Cai, Vanessa Helou, Angela L. Mazul, Dan P. Zandberg, Matthew E. Spector, Jose P. Zevallos, Robert L. Ferris, Kevin J. Contrera
Journal: Cancer Research (2025)

Abstract Importance: Neoadjuvant systemic therapy, including chemotherapy and immune checkpoint inhibitors, have potential benefits in head and neck squamous cell carcinoma (HNSCC). These potentially include reducing distant metastases, organ preservation, and treatment personalization. KEYNOTE 689 has the potential to change the treatment paradigm; however, trends in the use of neoadjuvant therapy leading up to the publication of this study remain unclear. Objective: To evaluate trends in the use of neoadjuvant systemic therapy in patients with HNSCC from 2015 to 2022. Design, Setting, and Participants: This retrospective, population-based cohort study utilized data from the National Cancer Database (2015-2021) to analyze neoadjuvant systemic and immunotherapy trends in HNSCC. Neoadjuvant treatment was defined as therapy administered at least 8 weeks prior to definitive surgery. Clinical staging and p16 status were assessed using AJCC 8th edition staging for patients diagnosed after 2018. Associations were analyzed using chi-square tests. Main Outcomes and Measures: The primary outcomes were trends in neoadjuvant therapy use and associations with tumor stage, anatomic site, and p16 status. Results: Among 292, 181 patients (216, 048 [74%] male; 76, 133 [26%] female), 922 received neoadjuvant systemic therapy, and 603 received neoadjuvant immunotherapy. Neoadjuvant therapy use began to rise in 2015 with an immunotherapy use rate of 0.078%, peaking at 0.325% in 2019 (a 4-fold increase) and stabilizing at 0.165% in 2022 (a 2-fold increase from 2015). Similarly, overall neoadjuvant chemotherapy use was 0.22% in 2015, 0.44% in 2019, and 0.26% in 2022. Sites with the largest increases in neoadjuvant immunotherapy use were the floor of mouth (3-fold), gums (2.4-fold), and tongue (2-fold). Patients receiving neoadjuvant therapy were significantly more likely to present with stage 4 disease compared to stages 1-3 (58% vs. 27%; P = .0005). p16 positivity rates were comparable between groups (84% vs. 80%; P = .68). Conclusions and Relevance: The use of neoadjuvant immunotherapy increased by 112% from 2015 to 2022, while overall neoadjuvant systemic therapy use rose by 18%. Patients undergoing neoadjuvant therapy were more likely to present with advanced-stage disease. With the upcoming release of KEYNOTE 689, understanding the current trends and treatment approaches for neoadjuvant therapy are crucial. Citation Format: Wesley L. Cai, Vanessa Helou, Angela L. Mazul, Dan P. Zandberg, Matthew E. Spector, Jose P. Zevallos, Robert L. Ferris, Kevin J. Contrera. Trends in use of neoadjuvant systemic therapy for head and neck squamous cell 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 2313.