Research areas

IRP (Integrated Research Program) 1

FRAP PDAC Resource Hub

Coordination: Rémy Nicolle (Team 14) & Audrey Vincent (Team 5)
Objective: To aggregate the network’s biological resources and public data (single-cell and spatial transcriptomics) within a FAIR hub — Findable, Accessible, Interoperable, Reusable — to accelerate pancreatic cancer research.
Hub structure:
- Pre-clinical hub: cataloguing and harmonizing models (PDO, PDX, CAF, etc.).
- Molecular data hub: aggregation, harmonization, and distribution of omics datasets.
- Patient/tissue hub: exploitation and valorization of biobanks and clinical collections.
Target users: network members (sensitive resources), academics (curated resources), and commercial entities.
The hub will rely on the BACAP national biobank infrastructure (INCa). Three full-time engineers will be dedicated to this effort.

Pre-clinical hub

Leader: Nelson Dusetti (Team 10)
Objective: To facilitate sharing, standardization, and quality control of preclinical models (PDO, PDX, CAF, primary cell lines) across laboratories.
Summary and rationale:
PDO, CAF, and PDX models are key tools for studying treatment response and resistance dynamics and for identifying predictive biomarkers. This work package aims to create a retrospective and prospective catalogue of network models, harmonize protocols, and implement a REDCap database compliant with OSIRIS standards.
Key actions:
- Build an inventory (core clinical data, processed multi-omics) stored in REDCap — pseudonymized and governed by the tissue committee.
- Harmonize production and characterization protocols (organoids, PDX, primary cultures) and implement them in Lille, Toulouse, and Marseille.
- Facilitate inter-team collaborations and knowledge sharing to increase model diversity.

Data hub

Leaders: Rémy Nicolle (Team 14) / Vera Pancaldi (Team 15)
Objective: To aggregate, normalize, and provide FAIR access to PDAC-related omics datasets, with integrated no-code analytical tools.
Summary:
Despite the availability of large datasets (>4k RNAseq patients, >2M scRNAseq), access and interoperability remain limited. The Data Hub will provide processed (level ≥3) datasets and associated clinical metadata, without storing identifiable raw data.
Planned functionalities:
- Aggregation, processing, curation, and normalization following OSIRIS standards; publication through a searchable web portal.
- No-code analysis hub: interactive applications (Shiny) enabling clinico-biological queries (survival analysis, scRNAseq exploration, spatial image interrogation).
- Modular development of applications tailored to network needs: gene expression by cell type, intercellular correlations, and spatial image features (tysserand, mosna).

Patient sample & tissue hub

Leaders: Jérôme Cros (Team 13) / Barbara Bournet (Team 9)
Objective: To centralize information on collections (tissue, blood, plasma) and facilitate access, processing, and valorization of samples.
Actions:
- Aggregate catalogue of partner collections, compliant with OSIRIS and published on the network portal.
- Provide access to the technical platform (histology, TMA, IHC, DNA/RNA extractions) to optimize sample use.
- Regulatory support through the tissue committee and logistic coordination between surgical and model production sites.

Leaders: Sophie Vasseur (Team 2) / Corinne Bousquet (Team 1)
Objective: Building on IRP1 resources, to develop fundamental and translational projects to better understand PDAC biology and address clinical needs.

Impact of the exposome

Leaders: Therese Truong (Team 7) / Nelson Jonckheere (Team 5)
Summary: Identification and validation of risk factors (diet, contaminants, air pollutants) associated with molecular subtypes of PDAC, through the E3N-Generations cohort and the BACAP biobank.
Main tasks:
- Identify risk factors (E3N cohort, questionnaires, GIS, biomonitoring).
- Validate findings biologically in vitro/in vivo (organoids, GEMM Pdx1-Cre;KrasG12D).

Cellular interactions within the tumor

Leaders: Corinne Bousquet (Team 1) / Richard Tomasini (Team 2)
Summary: Study the complex dialogue between cancer cells and the stroma (CAFs, endothelial, immune, and neural cells) within a rigid, hypoxic, and nutrient-poor microenvironment.
Tasks:
- Develop co-culture and tumor-on-chip models to study treatment resistance.
- Investigate cancer cell plasticity according to stage, location, resistance, treatment, and genotype.
- Decode the roles of soluble ligands, ECM, and EVs in tumor communication.

Impact of PDAC on the patient

Leaders: Sophie Vasseur (Team 2) / Stephane Servais (Team 6)
Summary: Study cancer-associated cachexia (CAC) and tumor-host interactions: metabolome, circulating signals, co-culture and GEMM models, and AI-based tools for CT-scan analysis.
Main tasks:
- Identify mechanisms leading to CAC and test therapeutic options.
- Investigate modulation of metastatic sites and changes in non-malignant parenchyma.
- Explore the role of the microbiome in tumor evolution and treatment resistance (PANORAMIX, CAPALONG).

Patient perspective

Leader: Cindy Neuzillet (Team 11)
Summary: Integrate patients’ priorities and needs (Espoir Pancreas survey, >3,000 respondents): quality of life, psychosocial impacts, and care pathways.
Tasks:
- Review HRQoL data collection in clinical trials and reanalyse PRODIGE trial data.
- Study psychosocial impacts on patients and caregivers (Psycho-Pancreas).
- Identify obstacles and enablers in care pathways to define relevant indicators.

Leaders: Cindy Neuzillet (Team 11) / Nelson Dusetti (Team 10)
Objective: To translate fundamental discoveries into therapeutic strategies and biomarkers integrated into clinical trials.

Biomarker-driven trials

Leaders: Nelson Dusetti (Team 10) / Jean-Baptiste Bachet (Team 12)
Key points:
- Validated and expanding predictive transcriptomic signatures (Predicting Med collaboration).
- Ongoing clinical trials: FUNGEMAX, GEMFOX, PACsign-01, GemSign-01, NeoPREDICT.
- Development of epigenetic signatures (ctDNA, piDNA) and dynamic plasma biomarkers.

New therapeutic modalities

Leaders: Pierre Cordelier (Team 9) / Ilaria Cascone (Team 3)
Focus areas:
- Improve drug delivery (lipidic and magnetic nanoparticles) and target resistance mechanisms (NUPR1, CDA).
- Immunomodulation approaches: magnetic nanoparticles, oncolytic viruses — assess safety and immune effects in syngeneic models.

Improving clinical trial design

Leaders: Cindy Neuzillet (Team 11) / Amelie Anota
Initiatives:
- Clinician–researcher–patient committee to co-design trials and ancillary studies.
- Define minimal datasets and PROs to be collected in trials.
- Develop clinically meaningful composite endpoints integrating the patient perspective.