tbuckley/cabot-search huggingface dataset:
Abstract 1577: PF-08046876: A new camptothecin antibody-drug conjugate directed to integrin beta-6 with potent antitumor activity in multiple preclinical solid tumor models
Authors: Rebecca C. Mazahreh, Narayana Yeddula, CB Lim, Gina LoMastro, Nicolas H. Garcia, Vineet Kumar, Christopher Frantz, Lauren Farr, Ryan Lyski, Lori Westendorf, Robert P. Lyon, Vivian H. Trang
Journal: Cancer Research (2025)

Integrins are a large family of cell surface receptors with diverse roles in cellular adhesion, motility, and cytokinesis. Functional integrins exist as heterodimers consisting of single alpha and beta chains. Within this family, integrin beta-6 (IB6), which dimerizes exclusively with integrin alpha-v, is a target of interest in the clinic for its role in cancer. IB6 expression is low in normal adult epithelial tissues and high in solid tumors. In some cases, high IB6 expression has been demonstrated to be associated with poor prognosis such as in non-small cell lung, colorectal, gastric and cervical carcinomas. PF-08046876 is an investigational antibody-drug conjugate (ADC) composed of an anti-IB6 antibody conjugated to a camptothecin-class topoisomerase I (TOPO1) inhibitor, AMDCPT, using a traceless enzyme-cleavable glucuronide linker. The AMDCPT payload was optimized for potency, reduced susceptibility to MDR efflux pumps and enhanced bystander activity. PF-08046876 leverages the same antibody backbone from Sigvotatug Vedotin (SV) and is specific for IB6 but does not bind other alpha-v family members. In preclinical studies, PF-08046876 has demonstrated activity in vitro and in multiple in vivo models spanning a range of antigen expression levels in several solid tumor carcinomas including non-small cell lung, head and neck squamous cell, urothelial, and pancreatic carcinomas. PF-08046876 demonstrates a tolerability profile in non-human primates that is consistent with camptothecin ADCs. These results suggest that PF-08046876 is promising ADC for the treatment of multiple carcinomas and supports further clinical investigation. A Phase 1, first-in-human study is planned to evaluate the safety and anti-tumor activity of PF-08046876. Citation Format: Rebecca C. Mazahreh, Narayana Yeddula, CB Lim, Gina LoMastro, Nicolas H. Garcia, Vineet Kumar, Christopher Frantz, Lauren Farr, Ryan Lyski, Lori Westendorf, Robert P. Lyon, Vivian H. Trang. PF-08046876: A new camptothecin antibody-drug conjugate directed to integrin beta-6 with potent antitumor activity in multiple preclinical solid tumor models [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 1577.
Abstract 3084: Claudin-11 promotes cisplatin resistance by inducing autophagy through activation of the PHF23-ERK signaling pathway in ovarian cancer cells
Authors: Ha Yeong Chae, So Young Lee, Hyojin Jeong, Hye Ri You, Jinil Han, Young Kee Shin, Mi Jeong Kwon
Journal: Cancer Research (2025)

Abstract Claudin-11, a member of claudins consisting of tight junction has been shown to be associated with prognosis and to play dual roles in cancer. However, its role in the response to anti-cancer agents is unknown. In this study, we investigated the role and mechanism of claudin-11 in cisplatin resistance in ovarian cancer. Kaplan-Meier survival analysis using The Cancer Genome Atlas data revealed that high CLDN11 expression is significantly associated with poor prognosis in ovarian cancer. Claudin-11 expression was significantly upregulated in cisplatin-resistant ovarian cancer cells. Consistent with this, claudin-11 overexpression significantly decreased the sensitivity to cisplatin in ovarian cancer cells. Cisplatin-induced apoptosis was reduced in claudin-11-overexpressing ovarian cancer cells, which was associated with decreased DNA damage. Moreover, claudin-11 overexpression inhibited cisplatin-induced apoptosis by promoting autophagy through increased ERK phosphorylation in ovarian cancer cells. The cisplatin sensitivity of claudin-11-overexpressing cells was restored by co-treatment with chloroquine, an autophagy inhibitor, and cisplatin, indicating that claudin-11 promotes cisplatin resistance by inducing autophagy. RNA sequencing data analysis further showed that autophagy-related PHD finger protein 23 (PHF23) is significantly upregulated in claudin-11-overexpressing cells compared with vector-transfected cells. PHF23 knockdown reversed cisplatin resistance by inhibiting ERK phosphorylation and then cisplatin-induced autophagy and apoptosis in claudin-11-overexpression cell. Taken together, these results indicate that claudin-11 promotes cisplatin resistance by activating autophagy through the PHF23-ERK signaling pathway and thereby reducing apoptosis in ovarian cancer cell, suggesting that inhibition of claudin-11 may overcome cisplatin resistance in ovarian cancer. Citation Format: Ha Yeong Chae, So Young Lee, Hyojin Jeong, Hye Ri You, Jinil Han, Young Kee Shin, Mi Jeong Kwon. Claudin-11 promotes cisplatin resistance by inducing autophagy through activation of the PHF23-ERK signaling pathway in ovarian cancer cells [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 3084.
Abstract 1825: Pharmacological evaluation of bioconjugated trastuzumab using the AbYlinkTM regio-selective conjugation technology in gastric cancer expressing HER2+
Authors: Céline Mothes, Peggy Provent, Marie Ruch, Mathieu Moreau, Michael Claron, Alex Helbling, Viktoriia Postupalenko, Léo Marx, Patrick Garrouste, Eftychia Koumarianou
Journal: Cancer Research (2025)

Abstract Purpose/introduction: Bioconjugation is a critical step in the development of Antibody Drug Conjugates with two main strategies dominating the field. One approach employs covalent chemistry to randomly bind a drug to the accessible Lysines or Cysteines on an antibody. The other strategy is site-specific, using covalent chemistry to bind a drug ligand at defined amino acid positions within the antibody. AbYlinkTM is a novel regio-selective labeling method for antibodies, enabling a single-step covalent conjugation of payloads such as radionuclide chelators to the Fc domain of an antibody. Given the selectivity of this reaction for the Fc region of the immunoglobulin, the affinity of the antibody to the antigen isn’t compromised, unlike randomly labelled antibodies. The chelators that are covalently attached to the antibody enable radiolabeling with radioisotopes such as Gallium-68, Lutetium-177 and Indium-111 for molecular radiotherapy or molecular imaging purposes. Experimental design: The commercially available trastuzumab was labeled via regio-selective conjugation with a DOTA-GA chelating agent using the AbYlinkTM technology, then radiolabeled with Indium-111. The in vivo biodistribution of the HER2 radiolabeled bioconjugate was evaluated in mice bearing NCI-N87 gastric cancer tumors. Results: Trastuzumab conjugation resulted in a homogeneous labeling of antibodies with a Degree of Conjugation (DoC) close to 2, conducted in a regio-selective manner. The biodistribution and imaging experiments demonstrated successful accumulation of the antibody within the NCI-N87 tumour implanted in mice. The radiolabeled conjugate remained stable in vitro and in vivo, demonstrating the AbYlink™ as a valuable tool for biologics conjugation. Conclusion: We have successfully validated in vivo the use of AbYlink™ technology in the context of Antibody Radio Conjugates. This regio-selective bioconjugation strategy holds potential for wider application across molecular radiotherapies or pharmacodynamic assessment of antibodies. Citation Format: Céline Mothes, Peggy Provent, Marie Ruch, Mathieu Moreau, Michael Claron, Alex Helbling, Viktoriia Postupalenko, Léo Marx, Patrick Garrouste, Eftychia Koumarianou. Pharmacological evaluation of bioconjugated trastuzumab using the AbYlinkTM regio-selective conjugation technology in gastric cancer expressing HER2+ [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 1825.
Abstract 1444: Wnt/β-catenin/TCF signaling suppresses GUCY2C hormone transcription by silencing p38
Authors: Ariana A. Entezari, Adi Caspi, Jasmine R. Alvarez, Jeffrey A. Rappaport, Adam E. Snook, Scott A. Waldman
Journal: Cancer Research (2025)

Sporadic colorectal cancers (CRCs) are initiated by APC mutations inducing aberrant β-catenin/TCF signaling regulating gene transcription. Similarly, the guanylyl cyclase C (GUCY2C) tumor suppressive axis is universally silenced in CRC. While the GUCY2C receptor is retained, transcriptional silencing of its paracrine hormones guanylin and uroguanylin by β-catenin/TCF signaling is among the earliest events in colorectal transformation. Moreover, suppression of the β-catenin/TCF pathway reconstitutes hormone expression. P38 is a tumor suppressor, and its loss promotes tumorigenesis in chemical and genetic mouse models of CRC. We aim to identify mechanisms by which β-catenin/TCF signaling silences the transcription of GUCY2C hormones to enable targeted reconstitution of ligand expression to prevent CRC. Here, we employed four human CRC cell lines with conditional β-catenin/TCF signaling and healthy human and mouse intestinal organoid models to explore the role of p38 in oncogenic transcriptional signaling. Indeed, toggling oncogenic β-catenin/TCF activity regulates p38 phosphorylation and downstream signaling, suggesting that β-catenin/TCF gain-of-function represses the p38 pathway. Further, pharmacological and genetic repression of p38 activity recapitulates β-catenin/TCF gain-of-function and directly eliminates GUCY2C hormone expression. Finally, beyond GUCY2C hormones, regulation of ∼80% of a core set of β-catenin/TCF-dependent genes common to human CRC cells is controlled by p38 signaling. Here, we reveal β-catenin/TCF regulation of p38 activity and its role in mediating transcriptional regulation of gene expression underlying nuclear oncogenic signaling in CRC. Citation Format: Ariana A. Entezari, Adi Caspi, Jasmine R. Alvarez, Jeffrey A. Rappaport, Adam E. Snook, Scott A. Waldman. Wnt/β-catenin/TCF signaling suppresses GUCY2C hormone transcription by silencing p38 [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 1444.
Abstract 2379: AptBCis2 plus pemetrexed for lung cancer leptomeningeal carcinomatosis and cancer-associated cachexia
Authors: Emily Pei-Ying Lin, Bo-Tsang Huang
Journal: Cancer Research (2025)

Abstract Introduction: Cancer-associated cachexia (CAC) is a multifactorial syndrome characterized by anorexia and body weight loss. CAC is associated with poor survival outcomes and is common in patients with advanced lung cancer, such as leptomeningeal carcinomatosis (LM). Treatment for lung cancer CAC and LM is challenging, and remains an unmet clinical need worthy of investigation. Aptamers are small synthetic oligonucleotides considered as antibody surrogates for targeted delivery. Here we report a novel aptamer-cisplatin conjugate, AptBCis2, which suppressed tumor progression and restored body weights in the mouse LM models. The effects were even more pronounced when combination regimens with AptBCis2 plus pemetrexed were used. Methods: The aptamer was identified via in vivo SELEX using a lung cancer LM orthotopic mouse model. The aptamer was conjugated with cisplatin to form AptBCis2. The tumor suppressive effects were investigated using mouse models. The AptBCis2 was administered through the tail vein; pemetrexed was injected intraperitoneally, and tumor burden was monitored via In Vivo Imaging System. The plasma and the CSF cisplatin concentrations were measured via Inductively Coupled Plasma Mass Spectrometry. Results: AptBCis2 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) alone or in combination with pemetrexed 100 mg/kg both showed superior tumor suppressive effects than cisplatin 2 mg/kg or pemetrexed 100 mg/kg monotherapy, as well as cisplatin 2 mg/kg plus pemetrexed 100 mg/kg combination therapy in lung cancer LM orthotopic mouse models. The treatments were given on day 2, 3, 5, 7, and 9 post tumor inoculation. On day 14 post tumor inoculation, percent of body weight change was about negative 20% in the cisplatin or cisplatin plus pemetrexed groups, positive 3% in the AptBCis2 group, and positive 20% in the AptBCis2 plus pemetrexed group (n = 8 in each group). The mice were sacrificed at day 14 for biochemical and image studies. Early mortality was observed on day 7 in the pemetrexed group with a negative body weight change of 20%. Conclusion: AptBCis2 in combination with pemetrexed showed not only tumor suppressive effects in lung cancer LM orthotopic mouse models but also restored mouse body weights during the treatment course. The data suggested potential roles of AptBCis2 plus pemetrexed in lung cancer LM and CAC. Citation Format: Emily Pei-Ying Lin, Bo-Tsang Huang. AptBCis2 plus pemetrexed for lung cancer leptomeningeal carcinomatosis and cancer-associated cachexia [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 2379.
Abstract 2347: A genetic test for skin cancer shows potential for accelerating early personalized chemoprevention in ultra-high risk transplant patients
Authors: Mathias Seviiri, Nirmala Pandeya, Catherine M. Olsen, Matthew H. Law, David C. Whiteman, Stuart MacGregor
Journal: Cancer Research (2025)

Abstract Background: Transplant patients are at extreme risk of multiple invasive skin cancers. Chemopreventive medication can reduce this risk by ∼50%, but clinicians are unable to identify high-risk patients before cancer onset. Objective: To assess the efficacy of a genetic test for skin cancer to identify ultra-high risk transplant patients who might benefit from chemoprevention or develop skin cancers with poor prognostic features. Methods: We developed a polygenic risk test for skin cancer using data from 1.2 million people using a Bayesian approach that models genetic information from the whole genome. We applied the genetic test to a cohort of transplant patients (STAR n=357) from a high UV environment in Australia to assess whether it could predict ultra-high risk individuals suitable for chemoprevention. Results: In the STAR cohort, higher genetic risk patients were more likely to: develop skin cancer (OR=2.04, 95%CI=1.54-2.71, P=8.72e-07), be treated with cancer-preventive medication (e.g. acitretin: OR=2.55, 95%CI=1.31 - 4.95, P=5.62e-03), have skin cancers with poor prognostic features, have poorly differentiated tumors (OR=2.29, 95%CI=1.39-3.77, P=1.18e-03), have tumors with unclear margins (OR=2.09, 95%CI =1.03-4.25, P=0.041), have large tumors &amp;gt;2cm (OR=4.09, 95%CI=1.88-8.90, P=3.92e-04), and have highly invasive disease (OR=1.95, 95%CI=1.18-3.23, P=9.06e-03). We are now conducting a comparative analysis in a large cohort (QSkin) of non-transplantees. Conclusion: Our genetic test for skin cancer has the potential to identify ultra-high risk transplant patients who should be prioritized by clinicians for personalized early chemoprevention. Citation Format: Mathias Seviiri, Nirmala Pandeya, Catherine M. Olsen, Matthew H. Law, David C. Whiteman, Stuart MacGregor. A genetic test for skin cancer shows potential for accelerating early personalized chemoprevention in ultra-high risk transplant 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 2347.
Late Relapse After Autologous Hematopoietic Stem Cell Transplantation in AQP4-IgG–Positive NMOSD
Authors: Nisa Vorasoot, Kyle M. Blackburn, Linda Nguyen, Melissa L. Bush, Sarah M. Jenkins, Jiraporn Jitprapaikulsan, James P. Fryer, Sarosh R. Irani, Eoin P. Flanagan, Sean J. Pittock
Journal: JAMA Network Open (2025)

This case series examines long-term outcomes for 2 aquaporin-4-IgG (AQP4-IgG)–positive patients with neuromyelitis optica spectrum disorder (NMOSD) who underwent autologous hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen and rituximab.
Abstract 2456: Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes predicts prognosis in gallbladder cancer after resection
Authors: Hyemin Kim, Young Hoon Choi, So Jeong Yoon Yoon, Cheolyong Joe, Se-Hoon Lee, Sang Hyun Shin, In Woong Han, Jin Seok Heo, Yo Han Jeon, Kee-Taek Jang, Kwang Hyuck Lee, Jong Kyun Lee, Kyu Taek Lee, Hongbeom Kim, Jookyung Sophie Park
Journal: Cancer Research (2025)

Abstract Background: Tumor-infiltrating lymphocytes (TIL) play an essential role in various cancer types. However, their prognostic significance in resected gallbladder cancer remains largely unknown. Methods: This study included 225 patients who underwent curative resection for gallbladder cancer. H&amp;E-stained whole slide images were analyzed using the Lunit SCOPE IO, an artificial intelligence (AI)-powered spatial TIL analyzer. Based on the density of intratumoral TILs in the cancer epithelium and stromal TILs in the cancer stroma, three immune phenotypes (IP) were defined: immune-inflamed phenotype (IIP), immune-excluded phenotype (IEP), and immune-desert phenotype (IDP). Survival outcomes were analyzed, with subgroup analysis conducted for early-stage (stage 0-II) and advanced-stage (stage III-IV) disease. Results: Of the 225 patients, 58 (25.8%) had IIP, 151 (67.1%) had IEP, and 16 (7.1%) had IDP. During a median follow-up of 71 months, 82 deaths (36.4%) were recorded. IIP and IEP were significantly associated with more prolonged disease-free survival (DFS) and overall survival (OS) compared to IDP. Conclusions: Immune phenotypes identified through AI-powered spatial TIL analysis were associated with DFS and OS in resected gallbladder cancer, particularly in late-stage disease. These findings highlight the prognostic potential of immune phenotyping, especially in advanced disease. Univariate and Multivariate Cox Regression Analyses for DFS and OS Citation Format: Hyemin Kim, Young Hoon Choi, So Jeong Yoon Yoon, Cheolyong Joe, Se-Hoon Lee, Sang Hyun Shin, In Woong Han, Jin Seok Heo, Yo Han Jeon, Kee-Taek Jang, Kwang Hyuck Lee, Jong Kyun Lee, Kyu Taek Lee, Hongbeom Kim, Jookyung Sophie Park. Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes predicts prognosis in gallbladder cancer after resection [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 2456.
Analysis of Surplus Cryopreserved Blastocysts in Fresh Donor Oocyte Cycles
Authors: Shelun Tsai, Xiaoyue Ma, Samantha Spring, Steven Spandorfer
Journal: JAMA Network Open (2025)

Importance Excess cryopreserved embryos present financial, logistical, and ethical constraints on patients and fertility clinics that are further complicated by the recently evolving US judicial landscape that may alter the legal status of frozen embryos and limit disposition options. It is therefore important to consider limiting the number of supernumerary embryos created from fresh donor oocytes. Objective To determine the optimal number of fresh donor oocytes to fertilize to achieve 1 live birth while minimizing supernumerary blastocysts. Design, Setting, and Participants This cohort study used data from recipients of fresh donor oocytes at member clinics of the Society for Assisted Reproductive Technology Clinic Outcomes Report System (SART CORS) between January 1, 2016, and December 31, 2020. Data were analyzed between August 2023 and June 2024. Main Outcomes and Measures The number of supernumerary blastocysts for a given number of fresh donor oocytes retrieved. Results There were 9395 fresh donor oocyte recipients included. The median (IQR) oocyte donor age at oocyte retrieval was 26 years (24-28 years), and the median (IQR) patient age at cycle start was 42 years (38-45 years). The median (IQR) number of oocytes retrieved was 20 (14-28), fertilized oocytes (2 pronuclei [2PN]) was 11 (7-17), usable embryos was 6 (3-10), and supernumerary blastocysts was 5 (2-8). When patients were divided evenly into quartiles based on the number of fresh donor oocytes retrieved (14 or fewer, 15 to 20, 21 to 28, 29 or more), it was associated with a significant increase in the number of cryopreserved supernumerary blastocysts (median [IQR] blastocysts by quartile: 2 [1-4] vs 4 [2-7] vs 6 [3-9] vs 9 [4-14], respectively; P &amp;amp;lt; .001). However, the live birth rate was lower only for those in the first quartile receiving 14 or fewer oocytes (50.8% [1207 of 2376] vs 64.1% [1497 of 2336] vs 67.9% [1631 of 2401] vs 67.9% [1550 of 2282]; P &amp;amp;lt; .001). Conclusions and Relevance In this retrospective cohort study of fresh donor oocyte cycles, the number of supernumerary blastocysts to achieve 1 live birth for a given number of fresh donor oocytes exposed to sperm was approximated, which may be valuable for counseling patients.