tbuckley/cabot-search huggingface dataset:
Abstract 4519: Lung carcinoma with air lucency: Possible classification and their prognosis
Authors: Kazuya Hisamatsu, Kazuhiko Shien, Shuta Tomida, Daisuke Mizuno, Ryota Fujiwara, Kousei Ishimura, Ryunosuke Fujii, Atsushi Matsuoka, Ryo Yoshichika, Tomoaki Higashihara, Naohiro Hayashi, Yuma Fukumoto, Kazuhiro Okada, Fumiaki Mukohara, Mao Yoshikawa, Ken Suzawa, Shinichi Toyooka
Journal: Cancer Research (2025)

Background: Lung cancer with air lucency (LCAL) represents a group of lesions in which a primary lung cancer manifests on CT images with a cyst or cystic airspaces. NSCLCs with adjoining cystic airspaces have been reported an increased risk of poor prognosis after surgical resection. However, the detailed classification of LCALs based on diagnostic imaging have not yet been established. We aim to classify LCALs into emphysematous and non-emphysematous groups objectively, and then analyze the prognosis of each group. Methods: A total of 101 surgically resected LCAL cases in our institution between 2015 and 2022 (including all cancer stages and histological subtypes) were collected. Cases were separated into emphysematous and non-emphysematous groups based on Goddard’s score, derived from LAA% (Low Attenuation Area percentages) analyzed in CT scans. A Goddard’s score of 1 or more was considered emphysematous in this study. Then, clinicopathological features and prognosis for each group were analyzed. Result: Sixty (59%) cases were classified as emphysematous, and forty-one (41%) cases as non-emphysematous. Higher pathological stages (worse than IIB) were more common in the emphysematous group (p-value&amp;lt;0.01). For respiratory performance (FEV1%), the emphysematous group had worse outcomes compared to the non-emphysematous group (p-value=0.01). Kaplan-Meier analysis revealed that the emphysematous group had a significantly worse overall survival (p-value=0.02). In multivariate analysis, a Goddard score of 1 or more, advanced TNM staging, and tumor histology subtypes other than adenocarcinoma were identified as independent risk factors for poor prognosis in LCAL patients. Conclusion: LCALs can be categorized using Goddard’s score into emphysematous and non-emphysematous groups, with the emphysematous group showing poorer overall survival. This result suggests that patients with emphysematous LCALs should be considered at high risk for poor outcomes following surgery. This classification may help identify patients who require alternative therapeutic strategies and/or more cautious post-operative management. Citation Format: Kazuya Hisamatsu, Kazuhiko Shien, Shuta Tomida, Daisuke Mizuno, Ryota Fujiwara, Kousei Ishimura, Ryunosuke Fujii, Atsushi Matsuoka, Ryo Yoshichika, Tomoaki Higashihara, Naohiro Hayashi, Yuma Fukumoto, Kazuhiro Okada, Fumiaki Mukohara, Mao Yoshikawa, Ken Suzawa, Shinichi Toyooka. Lung carcinoma with air lucency: Possible classification and their prognosis [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 4519.
Abstract 7301: FP011, A tri-specific immune checkpoint inhibitor targeting PD-1 × TIGIT × PVRIG for cancer immunotherapy
Authors: Yuanyuan Wang, Liang Xiao, Fan Wu, Baiguang Ren, Chang Zhou, Peipei Hu, Ke Chen, Xiaodong Wu, Di Lu, Yongting Huo
Journal: Cancer Research (2025)

Abstract Immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, have rapidly changed the treatment paradigm for multiple tumor types. Unfortunately, many patients still remain unresponsive or acquire resistance after initial response to treatment. The complex network of immunosuppressive molecules and their upregulation after initial treatment may contribute to such resistance, and lead to terminal exhaustion and fixed loss of effector functions of T cells. Here, we developed FP011, a tri-specific antibody which can simultaneously block the inhibitory signals of PD-1, PVRIG and TIGIT on effector T cells, so as to better activate T cells to kill tumor cells. In vitro, by interacting with T cells in cis, FP011 can act on T cells with higher avidity, exerting synergistic blockade of these three immunosuppressive signals. In a tri-target reporter assay, both FP011 and the combination group induced much stronger luminescence signal than those induced by bi-specific antibodies and monoclonal antibodies. In an antigen-specific (CMV) T cell activation assay, in which T cells were induced to exhaustion after long-term stimulation with CMV antigens, FP011 also induced a more significant degree of T cell activation than what bi-specific antibodies, pembrolizumab and the combination of anti-PD-1, anti-PVRIG and anti-TIGIT monoclonal antibodies could do. In a PBMC-engrafted NOD-dKO-A375 mice model, FP011 inhibited tumor growth (93%, P &amp;lt; 0.0001) in a way significantly better than anti-PD-1 antibody (39.45%, P = 0.0627), the combination of anti-PD1, anti-PVRIG and anti-TIGIT antibodies (90% P &amp;lt; 0.0001), and another tri-specific positive control (66.18%, P = 0.0007). The inhibition of tumor growth was associated with an increase of tumor-infiltrating T cells following the FP011 treatment. In conclusion, these data provide insight into the efficacy of FP011, both in vitro and in vivo, which indicates that targeting three immune checkpoints simultaneously can synergistically enhance T cell activation to achieve a better tumor-killing effect. Citation Format: Yuanyuan Wang, Liang Xiao, Fan Wu, Baiguang Ren, Chang Zhou, Peipei Hu, Ke Chen, Xiaodong Wu, Di Lu, Yongting Huo. FP011, A tri-specific immune checkpoint inhibitor targeting PD-1 × TIGIT × PVRIG 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 7301.
Abstract 5921: Correlation between MET amplification/overexpression status and response to MCLA-129 in advanced non-small-cell lung cancer (NSCLC): biomarker results from a phase 1 trial
Authors: Jie Wang, Jia Zhong, Yu Yao, Di Wu, Xiujuan Qu, Guojun Zhang, Haibo Zhang, Yu Cao, Zhuang Yu, Kai Chen, Maoqiong Jiang, Zhihua Li, Jianlin Long, Xiubao Ren, Huijuan Wang, Zhehai Wang, Lin Wu, Bolin Chen, Aimin Zang, Haie Chen, Lin Ma, Kan Liu, Peiqi Li, Lieming Ding
Journal: Cancer Research (2025)

Abstract Background: In this ongoing phase 1b study (NCT04930432) of the MET/EGFR bispecific antibody MCLA-129 in patients (pts) with advanced NSCLC, we aimed to gain a deeper insight into the relationship between MCLA-129 and efficacy in the MET amplification (METamp) or protein overexpression (OE) population. Methods: Eligible pts (≥18 years; ECOG PS 0-1; confirmed metastatic or unresectable NSCLC; and positive EGFR or MET alterations) received MCLA-129 (1500 mg biweekly) intravenously. MET OE was defined as IHC 2+/3+ and METamp was defined based on the gene copy number (GCN). Using a wide range of GCN cut-offs, we aimed to explore its relationship with efficacy outcomes.Results: At data cut-off (March 31, 2024), in 24 NSCLC pts, 6 with MET IHC 2+/3+ and 18 with METamp were evaluable for efficacy. Four out 6 pts with MET IHC 2+/3+ (median No. of previous lines: 1 [0-1]) achieved confirmed PRs (ORR: 66.7% [95% CI 22.3-95.7]), and all these 4 pts harbored concurrent mutations (3 METex14 skipping and 1 EGFR exon20ins). The median DOR and PFS were not reached. Eight out of 18 pts with METamp achieved confirmed PRs (median No. of previous lines: 2 [1-7]) (ORR: 44.4% [95% CI 21.5-69.2]; DOR: NR [2.8-NR]; PFS: 4.8 months [2.7-9.6]). Of 7 pts with METamp (METamp was detected prior to systemic antitumor therapy), 4 pts achieved confirmed PRs, with an ORR of 57.1% (95% CI 18.4-90.1), and all these 4 pts harbored concurrent mutations (2 EGFR exon20ins, 1 METex14 skipping and 1 L861Q). Among 9 pts that progressed on 3rd-generation EGFR-TKIs, 3 pts achieved confirmed PRs. Pts with different cut-offs of MET showed a differentiated ORR (Table). Conclusions: MCLA-129 showed clinically meaningful antitumor activity in advanced NSCLC with MET OE or METamp, particularly in pts with concurrent mutations. High GCN seemed to be associated with better efficacy in MET-amplified advanced NSCLC, suggesting its predictive properties. Citation Format: Jie Wang, Jia Zhong, Yu Yao, Di Wu, Xiujuan Qu, Guojun Zhang, Haibo Zhang, Yu Cao, Zhuang Yu, Kai Chen, Maoqiong Jiang, Zhihua Li, Jianlin Long, Xiubao Ren, Huijuan Wang, Zhehai Wang, Lin Wu, Bolin Chen, Aimin Zang, Haie Chen, Lin Ma, Kan Liu, Peiqi Li, Lieming Ding. Correlation between MET amplification/overexpression status and response to MCLA-129 in advanced non-small-cell lung cancer (NSCLC): biomarker results from a phase 1 trial [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 5921.
Abstract 5905: A non-invasive, methylation-based NGS assay for sensitive detection and monitoring of bladder cancer in urine
Authors: Feng Xie, Hang Dong, Haoran Tang, Yue Zhang
Journal: Cancer Research (2025)

Abstract Background: Bladder cancer, the sixth most common cancer worldwide, has a high recurrence rate, necessitating frequent and reliable disease monitoring. Current methods, such as cystoscopy, are invasive and can hinder patient compliance. However, detecting therapy response and disease progression on a molecular level still remains challenging. Urinary tumor DNA (utDNA) analysis offers a promising, non-invasive, and highly sensitive diagnostic tool for bladder cancer diagnosis and monitoring. By detecting utDNA methylation profiles, this analysis could enable personalized treatment decisions and improve clinical outcomes. Methods: We developed PredicineALERT, a methylation-based next-generation sequencing (NGS) assay designed for bladder cancer monitoring using urine. Methylation markers were identified through comparative analysis of profiles from bladder cancer patients and healthy donors. These markers were used to train a model capable of distinguishing bladder cancer from non-cancer samples. The assay's sensitivity and specificity were validated using serially diluted methylated DNA controls to determine its detection limit. To assess the performance of the PredicineALERT assay in detecting tumor fractions, serial urine samples were collected from muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant therapies and analyzed using both PredicineALERT and a tumor-informed minimal residual disease (MRD) assay. Results: A panel of methylation markers was identified from urine samples, enabling the model to accurately differentiate bladder cancer patients from healthy individuals. PredicineALERT demonstrated the ability to detect tumor signals at levels as low as 0.01%, underscoring its potential for minimal residual disease detection and early recurrence monitoring. Comparison with the tumor-informed MRD assay revealed excellent concordance in tumor fraction detection, further highlighting the assay's robustness and reliability. Conclusion: PredicineALERT is a non-invasive and highly sensitive assay for bladder cancer monitoring. Its design facilitates early recurrence detection while enhancing patient compliance, presenting a promising advancement in bladder cancer management. Citation Format: Feng Xie, Hang Dong, Haoran Tang, Yue Zhang. A non-invasive, methylation-based NGS assay for sensitive detection and monitoring of bladder cancer in urine [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 5905.
Abstract 4652: Prevalence and prognostic role of KDM6A deficiency and overexpression in surgically treated prostate cancer
Authors: Neele Heckmann, Natalia Gorbokon, Maximilian Lennartz, Martina Kluth, Eike Burandt, Till S Clauditz, Waldemar Wilczak, Stefan Steurer, Christian Bernreuther, Elena Bady, Lisa Hornsteiner, Ronald Simon, Hans Heinzer, Alexander Haese, Sarah Minner, Guido Sauter, Thorsten Schlomm, Markus Graefen, Florian Viehweger
Journal: Cancer Research (2025)

Abstract KDM6A, also known as UTX (ubiquitously transcribed X chromosome tetratricopeptide repeat protein) is a critical epigenetic regulator which is often subject to truncating mutations and subsequent expression loss in cancer. To interrogate the clinical significance of aberrant KDM6A expression, a tissue microarray containing prostate cancers from patients treated by prostatectomy was analyzed by immunohistochemistry. KDM6A immunostaining was weak in 33.5%, moderate in 52.9%, and strong in 7.3% of 13, 747 interpretable tumors while 880 (6.4%) tumors completely lacked KDM6A staining (KDM6A deficiency). The KDM6A status depended on the TMPRSS2:ERG fusion status. Strong KDM6A staining occurred in only 4.5% of ERG IHC negative, but in 11.1% of ERG IHC positive cancers while KDM6A deficiency occurred in 10.5% of ERG negative, but in only 1.4% of ERG positive cancers (p&amp;lt;0.0001 each). High KDM6A expression was linked to advanced pT, high Gleason grade, nodal positivity, and early PSA recurrence (p&amp;lt;0.0001 each). The prognostic role of high KDM6A expression was independent of pre- (Gleason score from biopsy, cT, PSA) and postoperatively (Gleason score from prostatectomy, pT, pN, R status) available parameters in all tumors (p&amp;lt;0.0001) and in ERG negative (p&amp;lt;0.0001) and positive subgroups (p=0.0049). In contrast, the outcome of KDM6A deficient cancers varied substantially between ERG negative (good prognosis) and ERG positive (bad prognosis) subgroups. In conclusion, the striking independent association of high KDM6A expression with poor prognosis suggests an important role of KDM6A expression in cancer cells which may have clinical utility in prostate cancer. The reciprocal role of KDM6A expression losses in ERG positive and negative cancers indicates a variable, cancer subtype dependent clinical effect of KDM6A deficiency. The clinical effects of anti-EZH2 drugs remains may depend on the ERG status in prostate cancer. Citation Format: Neele Heckmann, Natalia Gorbokon, Maximilian Lennartz, Martina Kluth, Eike Burandt, Till S Clauditz, Waldemar Wilczak, Stefan Steurer, Christian Bernreuther, Elena Bady, Lisa Hornsteiner, Ronald Simon, Hans Heinzer, Alexander Haese, Sarah Minner, Guido Sauter, Thorsten Schlomm, Markus Graefen, Florian Viehweger. Prevalence and prognostic role of KDM6A deficiency and overexpression in surgically treated prostate 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 4652.
Abstract 5934: Functional biomarkers for bladder cancer
Authors: Tianyu Yang, Karina Aguilar, Joshua van der Eerden, Vinata Lokeshwar
Journal: Cancer Research (2025)

Abstract Introduction and Objective: Urine tests could offer a less invasive method for identifying bladder cancer, including in patients with hematuria and history of bladder cancer. We previously discovered a first-in-class human Chondroitinase (Chase) that degrades chondroitin sulfate. This Chase is a splice variant of HYAL4 (V1) and promotes a malignant phenotype and chemoresistance in BC cells. The Chase test quantifies enzyme activity by measuring the degradation of chondroitin sulfate using an ELISA-like assay. We evaluated the efficacy of the Chase urine test in identifying bladder cancer. Methods: Test and validation cohorts came from three centers. The validation cohorts were prospective cohorts and assays were conducted in a blinded fashion. The cohorts included patients with microscopic and gross hematuria, benign genitourinary (BGU) conditions, history (HX) of BC or other genitourinary cancers (prostate and renal cell carcinoma). BGU cases included patients with BPH, cystitis, urinary tract infection, renal insufficiency, hematuria, urethral stricture, urolithiasis, and UPJ obstruction. V1 levels were measured by q-PCR and Chase activity by the Chase urine test. Results: Chase levels were significantly elevated in both low- and high-grade tumors, correlating strongly with BC across three cohorts (P&amp;lt;0.0001; OR: 4.4; 95% CI: 3.3-5.9). The Chase test demonstrated high sensitivity in detecting BC, regardless of grade. Similarly, HYAL-4 (V1) transcript levels were elevated in urine exfoliated cells (P&amp;lt;0.0001; OR: 1.5; CI: 1.3-1.7), with 83% sensitivity and specificity, increasing to 86% sensitivity at a lower threshold (79% specificity). In comparison, FDA-approved BTA and NMP22 tests showed &amp;lt;60% efficacy. In cohort 2, Chase achieved 84% accuracy in cases with atypical cytology, while cytology alone had 67% sensitivity and 96.6% specificity. Urinary Chase and HYAL-4 mRNA levels were 4-5 times higher in patients with BC during surveillance than in those without recurrence (P&amp;lt;0.0001). Conclusion: In test and validation cohorts Chase and V1 tests showed high sensitivity to detect BC and to monitor its recurrence. The Chase urine test is a less invasive alternative that could potentially reduce the need for cystoscopies for hematuria work-up and BC surveillance. Support: 1R01CA227277-05A1; 1R01CA283699-01 Citation Format: Tianyu Yang, Karina Aguilar, Joshua van der Eerden, Vinata Lokeshwar. Functional biomarkers for bladder 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 5934.
Abstract 6840: FGFR cell lines: A comprehensive approach to drug discovery and evaluation, from small molecules to biologics, covering binding to activation
Authors: Siyu Li, Yao Peng, Yu Wang, Maimaitiming Nuermanguli, Jinying Ning, Feng Hao
Journal: Cancer Research (2025)

Abstract Fibroblast growth factors (FGFs) bind to their receptors (fibroblast growth factor receptors, FGFRs), activating downstream signaling pathways, which play crucial roles in both mitogenic processes, such as embryogenesis and growth, and non-mitogenic processes, such as neuroregulation and metabolic regulation. FGFRs primarily consist of four subtypes: FGFR1, FGFR2, FGFR3, and FGFR4. Abnormalities like high expression or mutations in these receptors can lead to the aberrant activation of their signaling pathways, resulting in tumorigenesis. Consequently, targeting FGFR is a promising strategy for cancer therapy. Current FGFR-targeting drugs, either in clinical use or under development, include small molecule inhibitors, antibodies, antibody-drug conjugates (ADCs), CAR-T therapies, and soluble FGFR receptors. Different cell models are required for efficacy evaluation of various drug types. Kyinno has developed a comprehensive series of FGFR-related cell lines, which include Ba/F3 kinase cells, FGFR overexpression cells, knockout cells, and reporter cells. Among these, Ba/F3 cells have been meticulously engineered to depend on various FGFR point mutations and fusion mutations for survival, showcasing robust capabilities in evaluating FGFR small molecule inhibitors. The FGFR overexpression and knockout cells are crucial for assessing antibody binding, ADC drug endocytosis, and certain radioimmuno conjugates (RICs). Reporter cells, designed based on FGFR downstream signaling pathways, cover a spectrum of wild-type and point-mutated FGFR subtypes, thus effectively evaluating the impact of drugs on downstream signaling pathways. This strategic array of cell models collectively enhances the development and validation of FGFR-targeted therapies, providing invaluable insights and tools for advancing cancer treatment research. By leveraging these diverse cell models, researchers can better understand the mechanisms of FGFR-targeted interventions, ultimately contributing to more effective therapeutic strategies. Citation Format: Siyu Li, Yao Peng, Yu Wang, Maimaitiming Nuermanguli, Jinying Ning, Feng Hao. FGFR cell lines: A comprehensive approach to drug discovery and evaluation, from small molecules to biologics, covering binding to activation [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 6840.
Abstract 5383: Metabolic profiling of compressed stromal cells in the breast peritumor
Authors: Julian Najera, Hao Chen, Scott Howard, Meenal Datta
Journal: Cancer Research (2025)

Breast cancer represents a significant public health concern for women across the globe. Although the breast peritumor is increasingly recognized for its active role in modulating breast tumor growth and progression, its biophysical relationship with the tumor is poorly understood. Of particular interest is the effect of compressive forces imparted onto the peritumor by the growing mammary tumor. In this study, we found that compression metabolically reprograms stromal cells—namely, fibroblasts and adipocytes—found in the breast peritumor in vitro. Using fluorescence lifetime imaging microscopy, we discovered that fibroblasts and differentiated adipocytes under compression adopt a more glycolytic state whereas compressed pre-adipocytes appear to favor oxidative phosphorylation. We were able to confirm this metabolic shift in fibroblasts using bulk RNA sequencing, with pathway analysis showing that compressed fibroblasts significantly downregulate oxidative phosphorylation and strongly enrich glycolysis. Moreover, by measuring glucose uptake, we found that compression moderately increases glucose uptake in fibroblasts. Furthermore, through single cell transcriptomic analysis of breast cancer patients, we discovered that, in relation to those found in normal (compression (-)) tissue, fibroblasts and mature adipocytes in the peritumor (compression (+)) tend to favor glycolysis. It remains to be determined, however, to what degree this metabolic reprogramming is a direct consequence of external tumor compression. Citation Format: Julian Najera, Hao Chen, Scott Howard, Meenal Datta. Metabolic profiling of compressed stromal cells in the breast peritumor [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 5383.