tbuckley/cabot-search huggingface dataset:
Abstract 3500: LBL-054-CD3: An anti-CDH17 and CD3 bispecific antibody for the treatment of CDH17-positive gastrointestinal cancer
Authors: Xingxing Fang, Yurong Qin, Xiaoya Liu, Chengze Ni, Tingtng Li, Peng Zhang, Chao Chu, Mi Ye, Guojin Wu, Jianming Sun, Yue Zhao, Xiao Huang, Jordan Zhu, Shoupeng Lai, Xiaoqiang Kang, Hong Ling
Journal: Cancer Research (2025)

Abstract Background: CDH17 is a member of the cadherin superfamily, a group of calcium-dependent cell adhesion molecules critical for organ development, tissue integrity, and cancer progression. In normal tissues, CDH17 is highly restricted to the lateral membrane and concealed within intestinal tight junctions, making it inaccessible and blocking immune cell infiltration. In contrast, it is overexpressed and redistributed in 50% to 90% of gastrointestinal cancers, leading to its exposure on the cancer cell surface, therefore becoming more accessible to target. This unique feature makes CDH17 a promising target for T cell engager based immunotherapy for GI cancer. Here, we have developed a novel bispecific antibody, LBL-054-CD3, targeting CDH17 and CD3 to selectively kill CDH17-positive tumor cells by engaging T cells. Methods: LBL-054-CD3 was developed using our proprietary LeadsBody™ T-cell engager platform, comprising high-affinity arms targeting CDH17 and one finely tuned arm targeting CD3, engineered to balance efficacy and safety characteristics. The binding affinity of LBL-054-CD3 to CDH17 and CD3 was assessed using Fortebio, while its biological activity was evaluated through several cell-based assays, including reporter gene assay, TDCC to various levels of CDH17 expressing tumor cells, and T cell activation. The anti-tumor activity of LBL-054-CD3 antibody was evaluated in PBMC-humanized mice bearing GI tumor cell line xenograft models. Results: LBL-054-CD3 was shown potent binding affinity for CDH17 with no cross-reactivity to other family proteins. In vitro cytotoxicity assays revealed that LBL-054-CD3 mediated tumor cell killing was dependent on CDH17 expression level, inducing moderate cytokine release and cell proliferation while exhibiting no cytotoxic effects on CDH17-negative cells. In a PBMC-humanized mouse CDX model, LBL-054-CD3 demonstrated significant antitumor activity. Conclusions: The study demonstrates that LBL-054-CD3 has potent binding affinity to the membrane-proximal region of CDH17 and mediates T-cell cytotoxicity against various levels of CDH17 expressing tumor cells. Further, the bispecific antibody is shown excellent antitumor activity in both in vitro and in vivo experiments. Citation Format: Xingxing Fang, Yurong Qin, Xiaoya Liu, Chengze Ni, Tingtng Li, Peng Zhang, Chao Chu, Mi Ye, Guojin Wu, Jianming Sun, Yue Zhao, Xiao Huang, Jordan Zhu, Shoupeng Lai, Xiaoqiang Kang, Hong Ling. LBL-054-CD3: An anti-CDH17 and CD3 bispecific antibody for the treatment of CDH17-positive gastrointestinal 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 3500.
Abstract 3346: CD44 is an independent predictor of lymph node metastasis in differentiated thyroid cancer
Authors: Syed Zeeshan Qadri, Abdul K. Siraj, Sandeep K. Parvathareddy, Nabil Siraj, Padmanaban Annaiyappanaidu, Khawla S. Al-Kuraya
Journal: Cancer Research (2025)

Abstract Background: Differentiated Thyroid Carcinoma (DTC), a common endocrine malignancy, has witnessed a significant rise in global incidence over the past few decades. Despite its indolent nature and favorable prognosis, the clinical course of DTC varies extensively, with lymph node metastasis being an important risk factor in prognosis. CD44 has been shown to be associated with prognosis in various cancers. However, its role in DTC is not well explored. Methods: A total of 1703 DTC cases of Middle Eastern ethnicity were included in the study. CD44 expression was evaluated by immunohistochemistry using tissue microarray to analyze the clinico-pathological associations. Univariate and multivariate logistic regression analysis was used to determine the predictors of lymph node metastasis. Results: CD44 over-expression was noted in 69.7% (1187/1703) of DTC cases and was significantly associated with younger age (&amp;lt; 55 years; p &amp;lt; 0.0001), multifocality (p &amp;lt; 0.0001), lymphovascular invasion (p = 0.0007) and lymph node metastasis (p &amp;lt; 0.0001). Interestingly, on multivariate logistic regression analysis, CD44 was found to be an independent predictor of lymph node metastasis (Hazard ratio = 1.79; 95% confidence interval = 1.40 - 2.30; p &amp;lt; 0.0001). Conclusion: Our study showed that CD44 expression was an independent predictive biomarker of lymph node metastasis in Middle Eastern patients with DTC. Detection of CD44 expression could help identify patients at risk for developing lymph node metastasis and help in individualization of clinical management for DTC patients. Citation Format: Syed Zeeshan Qadri, Abdul K. Siraj, Sandeep K. Parvathareddy, Nabil Siraj, Padmanaban Annaiyappanaidu, Khawla S. Al-Kuraya. CD44 is an independent predictor of lymph node metastasis in differentiated thyroid 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 3346.
Abstract 2580: Direct interaction between cancer cells and fibroblasts drives epithelial-to-mesenchymal plasticity (EMP) and contribute to chemotherapy resistance
Authors: Nilu Dhungel, Ana- Maria Dragoi
Journal: Cancer Research (2025)

The tumor microenvironment (TME), composed of immune cells and fibroblasts, blood vessels, signaling molecules and extracellular matrix, provides important cues that govern epithelial-to-mesenchymal transition (EMT) and facilitate the acquisition of aggressive traits such as chemotherapy resistance by cancer cells. Cancer cells exist in multiple hybrid epithelial/mesenchymal (E/M) states responsible for the ever-changing environment during tumor development and metastasis. How are these hybrid states generated and maintained is not fully understood. Using small cell lung carcinoma (SCLC) and normal lung fibroblasts model we show that direct interaction between SCLC and lung fibroblasts induces a hybrid EMT phenotype in cancer cells in which several mesenchymal genes involved in receptor interaction with the extracellular matrix (ECM) and ECM remodeling are upregulated while epithelial genes such as E-cadherin remain unchanged. We also demonstrate that several core EMT-regulating transcription factors (EMT-TFs) are upregulated in cancer cells during direct contact with fibroblasts, including Yes-associated protein (YAP1), a major regulator of the Hippo pathway. Furthermore, we demonstrate that this upregulation of YAP1 in cancer cells which occurs significantly only during the direct interaction with fibroblast makes the cancer cells more resistant to chemotherapeutic agents resulting in more aggressive phenotypes. The cells become sensitive to chemotherapeutic agents when YAP1 is inhibited. Altogether, our results provide evidence that tumor cells’ direct contact with the fibroblasts in the TME initiates a signaling cascade responsible for hybrid E/M states of cancer cells. These hybrid states are maintained during the interaction and contribute to therapy resistance via YAP1 pathway, while interference with direct contact will result in slow recovery and a switch to the initial states. Citation Format: Nilu Dhungel, Ana- Maria Dragoi. Direct interaction between cancer cells and fibroblasts drives epithelial-to-mesenchymal plasticity (EMP) and contribute to chemotherapy resistance [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 2580.
Abstract 4025: Improving collaboration and well-being among patient advocates: lessons from Escape to THRIVE
Authors: Sherri Romanoski, Mindy Griffith, Brandi Forbes, Lisa Rezende
Journal: Cancer Research (2025)

Abstract Background: Patient advocates play a crucial role in supporting individuals with cancer, but advocates often face challenges related to collaboration, work-life balance, and burnout. Professional development opportunities, such as conferences, may help address these challenges, yet limited research exists on their long-term impact on patient advocates. Purpose: To evaluate changes in patient advocates' practices in three areas: 1) collaboration with other advocates, 2) work-life balance, and 3) self-care following participation in Escape to THRIVE, a leadership conference. Methods: Patient advocates attending the Escape to THRIVE conference in three different years (2020 (n=27), 2023 (n=21), and 2024 (n= 25)) were surveyed at three time points: pre-conference, immediately post-conference, and six or more months post-conference. Questions focused on collaboration with other advocates, workload management, and self-care behaviors. Responses were analyzed using both quantitative and qualitative methods. Results: Following conference participation, advocates demonstrated meaningful changes in collaboration and personal well-being management. A trend toward increased collaboration, with advocates more frequently partnering with those supporting patients with different cancer types. Participating advocates also reported improved workload management and self-care behaviors. Conclusion: Results suggest that targeted professional development at conferences can effectively promote positive changes in patient advocates' collaborative behaviors and personal well-being management practices, with benefits sustained over time. These findings support the value of professional development opportunities for patient advocates that promote professional collaboration and personal well-being management. Citation Format: Sherri Romanoski, Mindy Griffith, Brandi Forbes, Lisa Rezende. Improving collaboration and well-being among patient advocates: lessons from Escape to THRIVE [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 4025.
Abstract 4374: Discovery of a highly potent and efficacious SOS1 inhibitor targeting KRAS-driven cancers
Authors: Yang Li, Yang Zang, Wenbing Hu, Yuan Zhou, Lifei Liu, Xuejun Zhang, Shaohua Chang
Journal: Cancer Research (2025)

Abstract SOS1 is a crucial protein that activates RAS by promoting its conversion from the inactive GDP-bound state to the active GTP-bound state, triggered by growth factor receptor signals. This process is further enhanced by a feedback mechanism between SOS1 and RAS, increasing the strength and duration of RAS signaling, making SOS1 a significant therapeutic target in the RAS-MAPK pathway. Genetic alterations in the RAS-MAPK pathway are frequently observed across a spectrum of cancer types. While therapies targeting KRAS G12C mutations has been approved for certain types of lung cancers, there remains a need for treatments addressing other mutations (e.g. KRAS G12D, G12V etc.). Inhibiting SOS1 has shown potential in reducing proliferation of cancer cells dependent on KRAS signaling. Here, we report the discovery of a highly potent and efficacious SOS1 inhibitor HW071021. It demonstrates an IC50 of 8.5 nM in SOS1 binding assay and modulates ERK1/2 phosphorylation (pERK) in DLD-1 cell assay. Oral administration of HW071021 as a monotherapy in mouse MIA PaCa-2 xenograft models harboring KRAS G12C mutations results in significant tumor growth inhibition (TGI:∼78%). Additionally, HW071021 combination with the EGFRi Osimertinib demonstrated much greater antitumor activity than Osimertinib monotherapy (TGI: 97% vs 33%) in mouse NCI-H1975 (EGFR L858R/T90M) xenograft model. HW071021 has excellent ADME and physical properties with low risks of hERG-related cardiotoxicity and drug-drug interactions . These data support the clinical utility of HW071021 as a single agent or combination partner of Osimertinib for the treatment of human Kras-driven cancers. IND application in China has been approved in September. Citation Format: Yang Li, Yang Zang, Wenbing Hu, Yuan Zhou, Lifei Liu, Xuejun Zhang, Shaohua Chang. Discovery of a highly potent and efficacious SOS1 inhibitor targeting KRAS-driven cancers [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 4374.
Abstract 2427: Optimization of preprocessing strategies for developing AI-based disease diagnosis model using whole transcriptomic data
Authors: Ki Wook Lee, Hye Jung Min, Hyun Woo Park, Balachandran Manavalan, Young-Jun Jeon
Journal: Cancer Research (2025)

Abstract Current research in medicine and biology predominantly focuses on applying artificial intelligence (AI) to analyze patient-specific imaging data, such as CT and MRI scans. However, the application of AI to next-generation sequencing (NGS) data, particularly transcriptomics, remains underutilized. RNA sequencing data is prone to biological and technical variability during generation, and the choice of error-correction and preprocessing methods can significantly influence downstream analyses. These challenges underscore the need for clear and systematic guidelines to optimize transcriptome data for AI-based analyses. In this study, we aim to identify optimal preprocessing strategies for developing AI models leveraging transcriptomic data. We utilized RNA sequencing datasets from 25 independent cohorts, comprising over 5, 800 patients with conditions such as lung adenocarcinoma, colorectal cancer, diabetes, and other diseases. A total of 18 combinatorial preprocessing pipelines were systematically assessed, encompassing 6 normalization methods (Raw, CPMTMM, RLE, UQ, RPKM, TPM) and 3 scaling methods (None, MinMax, Z-score). Over 20, 000 transcripts were processed using each combination of normalization and scaling techniques. We then developed disease diagnosis models using 13 machine learning and deep learning algorithms. The performance of these models was evaluated to identify the most effective preprocessing strategies for transcriptomic data. We identified algorithm-specific optimal preprocessing strategies to develop robust AI models utilizing transcriptomic data. Performance variations driven by normalization and scaling methods were observed for each algorithm, with these differences being particularly pronounced in datasets characterized by inherently lower model performance (difficult tasks). Our findings underscore the critical role of preprocessing in shaping model outcomes and provide a foundation for the development of tailored AI frameworks for disease diagnosis. This study offers a systematic approach to optimize transcriptomics-based predictive modeling, advancing the integration of AI into transcriptomic data analysis for clinical applications. Citation Format: Ki Wook Lee, Hye Jung Min, Hyun Woo Park, Balachandran Manavalan, Young-Jun Jeon. Optimization of preprocessing strategies for developing AI-based disease diagnosis model using whole transcriptomic data. [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 2427.
Abstract 2931: AXL-directed surface targeting approaches in recalcitrant pulmonary high-grade neuroendocrine carcinomas
Authors: Kavya Ramkumar, C. Allison Stewart, Yan Yang, Bingnan Zhang, Qi Wang, Yuanxin Xi, Runsheng Wang, Alejandra G. Serrano, Luisa M. Solis Soto, Jing Wang, John V. Heymach, Carl M. Gay, Lauren A. Byers
Journal: Cancer Research (2025)

High-grade neuroendocrine carcinomas of the lung (hgNECs), which include small cell lung cancer (SCLC) and pulmonary large-cell neuroendocrine carcinoma (LCNEC), are characterized by poor prognoses, limited treatment options and rapid emergence of resistance. While recent surfaceome-directed approaches targeting DLL3, SEZ6, and TROP2 using chimeric antigen receptor T cells (CAR-Ts), bispecific T cell engagers (BiTEs) and antibody drug conjugates (ADCs) show considerable promise in hgNECs, novel strategies to target the heterogenous resistant disease are needed. AXL, a TAM family receptor tyrosine kinase, is known to mediate resistance to chemotherapy, radiation and targeted therapies in SCLC and other cancers, through its roles in epithelial to mesenchymal transition (EMT), DNA damage repair and replication stress tolerance. We hypothesize that targeting cell surface AXL would provide an effective therapeutic strategy in hgNECs, especially for relapsed disease. We analyzed the transcriptomic (bulk and single-cell RNA sequencing) and proteomic (immunohistochemistry) expression profiles of AXL in treatment-naïve and relapsed SCLC, LCNEC and other extrapulmonary hgNECs patient tumors. High levels of AXL expression were seen in distinct tumor subsets. Notably, AXL-high tumors exhibited molecular signatures associated with resistance (higher EMT scores, lower replication stress and cisplatin response). To evaluate AXL as a viable surface target in hgNECs, we generated a preclinical CAR T cell against AXL. Anti-AXL CAR T cells were effective at inducing cytotoxicity in AXL-expressing SCLC and LCNEC cell lines. Similarly, an anti-AXL ADC also showed selective and potent cytotoxicity in AXL-positive models. These findings establish AXL as both a valuable biomarker and a promising target for the drug-resistant hgNECs, supporting the development of AXL-directed therapeutics such as anti-AXL CAR T cells and anti-AXL ADCs. Citation Format: Kavya Ramkumar, C. Allison Stewart, Yan Yang, Bingnan Zhang, Qi Wang, Yuanxin Xi, Runsheng Wang, Alejandra G. Serrano, Luisa M. Solis Soto, Jing Wang, John V. Heymach, Carl M. Gay, Lauren A. Byers. AXL-directed surface targeting approaches in recalcitrant pulmonary high-grade neuroendocrine carcinomas [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 2931.
Abstract 4031: Project Cure CRC: advancing precision medicine in colorectal cancer through innovative research and targeted therapies
Authors: Kimberly Lynn Newcomer, David Fenstermacher
Journal: Cancer Research (2025)

Abstract Background: The Colorectal Cancer Alliance founded Project Cure CRC to support breakthrough research in colorectal cancer (CRC) and advance precision medicine to improve patient outcomes. CRC remains one of the most common and deadly cancers, with over 1.9 million new cases and 935,000 deaths annually. A significant challenge in CRC treatment is the genetic variability among patients, leading to different responses to standard therapies and highlighting the need for personalized approaches. Many CRC cases involve mutations that resist conventional treatments, resulting in poor prognosis and limited options for affected patients. Methods: Project Cure CRC launched a targeted Request for Proposals (RFP) to address these challenges based on insights from last year’s Cure CRC Summit. The RFP attracted 250 proposals centered on novel precision medicine strategies, and nearly $7 million in funding has been allocated to support 18 high-impact research projects. Results: Funded projects employ diverse and innovative strategies to tackle CRC. Critical approaches include enhancing intratumoral mRNA vaccines that target immune checkpoints to boost anti-tumor responses and combining targeted radiation with immunotherapies to create synergistic effects in advanced CRC. Additional studies focus on new drug combinations for BRAF-mutated CRC, which has low response rates to existing treatments. Other projects investigate ProAgio, a protein targeting cells that support cancer survival, with the potential to improve therapies for hard-to-treat tumors. Further research examines how fat tissue influences CRC growth and metastasis, particularly in patients with obesity, and leverages technology to target multiple genes simultaneously, identifying cancer cell vulnerabilities and enhancing immune response. The Alliance has also funded a theranostic project that is able to use the same drug molecule to determine the location of tumors and a target therapeutic approach, and the development of a drug pipeline platform that will accelerate the development of new targets and therapies. Conclusions: These initiatives demonstrate the Alliance’s commitment to advancing precision medicine and addressing key gaps in CRC care, particularly for patients with treatment-resistant profiles. By funding high-impact research and fostering collaboration, Project Cure CRC aims to accelerate the development of personalized, effective treatments for CRC patients, transforming the landscape of colorectal cancer care. Citation Format: Kimberly Lynn Newcomer, David Fenstermacher. Project Cure CRC: advancing precision medicine in colorectal cancer through innovative research and targeted therapies [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 4031.
Abstract 2543: Dynamic whole-body PET/CT can predict the treatment response to chemoradiotherapy of esophageal cancer patients
Authors: Yoshihiro Kurata, Moe Iwata, Koichi Hayano, Yasunori Matsumoto, Ryota Otsuka, Akira Nakano, Tadashi Shiraishi, Nobufumi Sekino, Toyozumi Takeshi, Masaya Uesato, Gaku Ohira, Hiisahiro Matsubara
Journal: Cancer Research (2025)

Abstract Background: Majority of positron emission tomography-computed tomography (PET/CT) studies are based on static images. However, dynamic whole-body PET-CT (DW-PET/CT) enables quantification of tissue glucose metabolism dynamics. The purpose of this study is to investigate whether DW-PET/CT can predict the treatment response in esophageal squamous cell carcinoma (ESCC) patients treated with chemoradiotherapy (CRT). Methods: Fifty ESCC patients who underwent pretreatment DW-PET/CT were evaluated. DW-PET/CT parameters of the main tumor including Patlak slope (PS, absolute rate of tracer consumption) and Patlak intercept (PI, degree of tracer perfusion in the tumor) were calculated using 4 whole-body PET/CT image series acquired at every 5 minutes from 60 minute after injection of 18F-fluorodeoxyglucose. The maximum standardized uptake value (SUVmax) of the tumor was also measured at 60 minute of the tracer injection. The relationships of these PET derived parameters with treatment response was analyzed. Results: Treatment responders were 34 patients, while non-responders were 16 according to the RECIST criteria. Tumors of responders showed significantly higher SUVmax, PS and PI than non-responders (P=0.03, 0.0003, 0.001, respectively). PS and PI showed a good performance to predict the treatment response with AUC of 0.75 and 0.79, whereas SUVmax showed a poor performance with AUC of 0.69. Tumor contraction rate during CRT showed significant positive correlation with PS and PI (P=0.005, 0.03, respectively). Conclusions: DW-PET/CT might enable pretreatment prediction for the treatment response to CRT in ESCC patients. Citation Format: Yoshihiro Kurata, Moe Iwata, Koichi Hayano, Yasunori Matsumoto, Ryota Otsuka, Akira Nakano, Tadashi Shiraishi, Nobufumi Sekino, Toyozumi Takeshi, Masaya Uesato, Gaku Ohira, Hiisahiro Matsubara. Dynamic whole-body PET/CT can predict the treatment response to chemoradiotherapy of esophageal cancer patients [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 2543.