Nelson Dusetti, Head of the Translational Research and Innovative Therapies Department at the Cancer Research Centre of Marseille (CRCM), shared a post on LinkedIn about a recent article he and his colleagues authored:
“New preprint on bioRxiv.
Most therapies in PDAC ignore the stromal context, focusing only on tumor genetics. This study shows that genotype and stroma are inseparable: targeting both could open a new precision medicine avenue.
This work highlights the need to design dual therapeutic strategies combining DNA damage-targeted treatments with stromal modulation. A step toward truly personalized therapies in pancreatic cancer.
Pancreatic cancers with ATM loss (a frequent DNA repair defect) don’t just have epithelial vulnerabilities, they also reprogram their tumor microenvironment.
Through a ROS-TGF-β axis, ATM-deficient tumors drive fibroblasts into a myCAF state that fuels fibrosis, invasiveness, and chemoresistance. To elevated ROS to increased TGF B and finally myCAF enrichment myCAFs equals to denser fibrosis plus drug resistance TGF-β inhibition reverses this phenotype and improves chemotherapy response in preclinical models
This work is the result of an important collaboration between CRCM – Centre de Recherche en Cancérologie de Marseille Institut Paoli-Calmettes (IPC), the Ulm University team led by Alexander Kleger, and international partners.”
Title: Exploiting TGF-β-mediated Stromal Programming in Homologous. Recombination-Deficient Pancreatic Cancer
Authors: Elodie Roger, Hannah M. Mummey, Eleni Zimmer, Dharini Srinivasan, Anna Härle, Loïc Moubri, Alica K. Beutel, Rima Singh, Menar Ekizce, Michael K. Melzer, Yun Lee, Austin Silva, Luisa Härle, Thomas Engleitner, Frank Arnold, Mareen Morawe, Benjamin Naggay, Juliane Schneider, Leonard Gilberg, Julia P. Mosler, Christina Ludwig, Chen Meng, Maximilian Hirschenberger, Victoria Hunszinger, Klaus Kluck, Martina Kirchner, Anna-Lena Volckmar, Mareike Wirth, Mohamed S.S. Alhamdani, Jörg D. Hoheisel, J.-Matthias Löhr, Thomas Seufferlein, Alireza Abaei, Ralf Kemkemer, Roland Rad, Jan Budczies, Medhanie A. Mulaw, Patrick C. Hermann, Mark Hänle, Konstantin M. J. Sparrer, Christopher J. Halbrook, Kyle J. Gaulton, Konrad Steinestel, Albrecht Stenzinger, Nelson Dusetti, Lukas Perkhofer, Johann Gout, Alexander Kleger.
Read the Full Article in bioRxiv.
More posts featuring Nelson Dusetti on OncoDaily.