Nelson Dusetti, Head of the Translational Research and Innovative Therapies Department at the Cancer Research Centre of Marseille (CRCM), shared a post on LinkedIn:
“We are pleased to share our collaborative publication in Advanced Science:
“Decoding the Integrated Stress Response of Pancreatic Cancer: Identifying a Serine-dependent Tumor Subset Under Metabolic Relationships With CAFs.”
Transcriptomic classifications of pancreatic ductal adenocarcinoma (PDAC) have significantly refined prognostic stratification, but they still fall short of defining actionable personalized therapies.
In this study, tumors were stratified based on mRNA translation rates, a functional layer of gene expression frequently altered in cancer but rarely used for classification. This approach revealed a distinct PDAC subtype characterized by:
- Low global protein synthesis
- Activation of the Integrated Stress Response (ISR)
- Resistance to chemotherapy and apoptosis
- Serine auxotrophy due to altered serine and cysteine biosynthesis pathways
Importantly, this vulnerability is associated with improved overall survival in patients and is sustained through a metabolic symbiosis with cancer-associated fibroblasts (CAFs), which may supply serine to support tumor growth.
Our team contributed PDAC patient-derived models and participated in transcriptomic and functional analyses, helping to validate this subtype biologically and to characterize tumor–stroma metabolic interactions.
Why is this important?
This work refines PDAC classification beyond conventional transcriptomic subtypes by integrating a functional translational layer. It demonstrates that translatomic profiling can identify resistant tumor subsets while uncovering actionable metabolic dependencies within the tumor microenvironment.
These findings open the door to new therapeutic strategies targeting metabolic crosstalk between tumor cells and CAFs, a potentially druggable vulnerability in a disease still lacking effective precision approaches.
A very special thank you to Yvan Martineau for his trust and for a truly productive and intellectually stimulating collaboration.
Congratulations to all co-authors involved.”
Title: Decoding the Integrated Stress Response of Pancreatic Cancer: Identifying a Serine-dependent Tumor Subset Under Metabolic Relationships With CAFs.
Authors: Sauyeun Shin, Mehdi Liauzun, Jacobo Solorzano, Morgane Le Bras, Christine Jean, Benjamin Fourneaux, Margaux Dore, Lea Fevrier, Ismahane Belhabib, Alexia Brunel, Cindy Neuzillet, Marion Larroque, Carine Joffre, Stephane Rocchi, Nicolas Fraunhoffer, Aurelie Perraud, Muriel Mathonnet, Vera Pancaldi, Laetitia Linares, Juan Iovanna, Nelson Dusetti, Ola Larsson, Remy Nicolle, Stephane Pyronnet, Corinne Bousquet, Yvan Martineau
Read the Full Article.
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