Metabolic Reprogramming and Microenvironment in Pancreatic Adenocarcinoma

Metabolic Reprogramming and Microenvironment in Pancreatic Adenocarcinoma: Identification of New Therapeutic Targets

The present project aims to elucidate the metabolic interactions within the tumor microenvironment of pancreatic adenocarcinoma, both in the primary tumor and in hepatic and pulmonary metastatic sites, as well as in circulating blood biomarkers.

Deciphering these complex interactions aims to identify exploitable vulnerabilities for predicting treatment efficacy or for guiding therapeutic strategies.

Pancreatic adenocarcinoma (PDAC) remains one of the deadliest cancers, with survival rarely exceeding a few months and limited progress despite improved chemotherapy. Its poor prognosis is driven by late diagnosis, therapeutic resistance, and low responsiveness to targeted therapies and immunotherapy.

PDAC is characterized by a dense, immunosuppressive stroma and severe metabolic stress due to poor vascularization. Tumor progression relies heavily on stromal cells-such as cancer-associated fibroblasts and macrophages-as well as metabolic adaptations of cancer cells.

This project focuses on two key PDAC features to identify new biomarkers and therapeutic targets:

• Stromal cell prevalence
• Metabolic reprogramming

Inclusion Criteria:

1. Age > 18 years

2. Signed written informed consent specific to the PROMETAP study

3. Affiliation with a social security system

4. Treatment and follow-up performed at the Institut Paoli-Calmettes

5. Metastatic PDAC requiring biopsy as part of routine care (group1 and 2)

6. Prior treatment:

   • No previous chemotherapy for the "initial" group
   • No prior chemotherapy in the metastatic setting for the "Metastatic Relapse" group

7. Eligible for chemotherapy (ECOG < 2)

Non-Inclusion Criteria:

1. Contraindication to biopsy of the pancreatic tumor or a hepatic or pulmonary metastasis (group 1 and 2)
2. Absence of a metastasis accessible to biopsy (group1 and 2)
3. Concurrent treatment for another active cancer
4. Pregnant or breastfeeding women
5. Patients in emergency situations

5. Adult individuals under legal protection (guardianship, trusteeship, judicial protection) or unable to provide informed consent