Post by Robert Bosch Center for Tumor Diseases

We are pleased to share the publication of a new study in Gut that provides clinically relevant mechanistic insights into therapy resistance in pancreatic ductal adenocarcinoma (PDAC). This work represents a long-standing, highly productive collaboration with the group of Professor Dr. Volker Ellenrieder at the Universitätsmedizin Göttingen, together with the Johnsen and Najafova research groups at the Robert Bosch Center for Tumor Diseases (RBCT). The study exemplifies the cooperative research model of the RBCT, integrating mechanistic cancer biology, clinically annotated patient cohorts, and advanced patient-derived model systems across institutional boundaries. In this study, the authors identify a clinically aggressive PDAC subgroup defined by high nuclear activity of GSK3β and NFATc1. Mechanistically, this signaling axis promotes homologous recombination–mediated DNA repair, thereby driving resistance to platinum-based chemotherapy. Importantly, targeted disruption of the GSK3β–NFATc1 pathway restores platinum sensitivity across multiple preclinical platforms, including patient-derived cells, organoids, ex vivo tumor explants, and in vivo models. From a translational and clinical perspective, these findings define a biologically and clinically actionable PDAC subgroup that combines poor prognosis with a clear therapeutic vulnerability. The work provides a strong rationale for biomarker-guided patient stratification and the development of subgroup-adapted combination strategies integrating pathway-directed interventions with established platinum-based regimens. As such, it directly informs the design of future stratification-based clinical trials and aligns closely with the RBCT’s strategic focus on translating molecular mechanisms into clinically meaningful treatment concepts. ⸻ ⭐ Publication details ⭐ Muhammad Umair Latif, Xuean Liu, Aiko Bockelmann, Laura Huhnold, Geske Schmidt, Lukas Klein, Xueyuan Zhao, PD Dr. Dr. Lena-Christin Conradi (MD, PhD), Karly Conrads, Anna Lena Weber, Sercan Mercan, Kristina Reutlinger, Atmika Paul, Zeynab Najafova, Prof. Dr. Steven A. Johnsen, Zuriñe Bonilla Del Rio, Frederike Penz, Jovan Todorovic, Holger Bastians, Tim Beissbarth, Ulrich Sax, Ramy Ashry, Oliver H. Krämer, Elisabeth Hessmann, Günter Schneider, Prof. Dr. med. Philipp Ströbel, Ivan Bogeski, Shiv K. Singh, Ph.D., Volker Ellenrieder GSK3βhigh/NFATc1high subgroup targeting overcomes therapy resistance in pancreatic cancer through transcriptional induction of homologous recombination repair Gut (2025) DOI: 10.1136/gutjnl-2025-336227 https://lnkd.in/dk7nqhCJ Bosch Health Campus Robert Bosch Stiftung #PancreaticCancer #PDAC #TranslationalResearch #PrecisionOncology #ClinicalResearch #PatientStratification #TherapyResistance #CollaborativeResearch #UniversityMedicine #KFO5002