PancDEMIC Program: Gaining a Better Understanding of the Mechanisms Underlying the Onset, Progression, and Treatment Resistance of Pancreatic Cancer

Pancreatic cancer is one of the most aggressive forms of cancer. In France, approximately 16,000 new cases are diagnosed each year, and its incidence has increased in recent years, according to figures from the National Cancer Institute. The prognosis remains particularly poor, with a five-year survival rate of 11%.

This situation is largely due to late diagnosis—often at an advanced stage—and the limited effectiveness of available treatments. Even when the tumor is operable, the risk of recurrence remains high, indicating early dissemination of tumor cells.

Biologically, pancreatic cancer is characterized by high heterogeneity and a complex tumor microenvironment, which contribute to its resistance to treatment. In the majority of cases, the disease is linked to a mutation in the KRAS gene, which plays a central role in the development and progression of the cancer.

Despite recent advances, notably the emergence of KRAS-targeting inhibitors, the mechanisms governing the onset of the disease, its progression, and resistance to treatment remain poorly understood.

Furthermore, certain forms of the disease are diagnosed at a younger age, though the factors explaining this have not yet been clearly identified. This trend raises questions about the possible role of lifestyle or environmental factors, even though their exact contribution has yet to be determined. These factors underscore the need for research that integrates biological, clinical, and contextual data.

The PancDEMIC program draws on the study of patients with localized forms of the disease to analyze, within a structured clinical setting, the biological mechanisms involved in disease progression and response to treatment.

The primary objective is to establish an infrastructure for collecting and analyzing biological samples and clinical data.

The program focuses in particular on:

• Understanding how tumors develop and evolve over time. 

• Analyzing the impact of treatments, particularly KRAS inhibitors, on tumor cells.

• Identifying early mechanisms of treatment resistance. 

• Detecting biomarkers that can better predict disease progression and treatment response. 

The program also aims to organize and share data across multiple research teams to facilitate cross-analysis. This approach should enable better use of patient samples and maximize their scientific value.

Ultimately, this research should help improve early detection, refine treatment strategies, and develop more personalized approaches.

PancDEMIC is based on a structured medical-scientific platform organized around the systematic collection of samples and data from patients with localized pancreatic cancer.

The program is closely linked to the POWER clinical trial, a Phase II study evaluating several preoperative therapeutic strategies in patients with operable pancreatic cancer. Among these is daraxonrasib, a therapy targeting alterations in the RAS/KRAS pathway, which has already shown very encouraging results in metastatic forms of the disease and whose potential will now be explored in localized disease.

As part of this trial, samples are collected at various points during the course of care:

• Before treatment begins.

• During treatment.

• At the time of surgery.

• And, when possible, during follow-up.

These samples are linked to detailed clinical data, making it possible to correlate the tumor’s biological progression with the patient’s characteristics and response to treatment.

The analyses are based on multi-omic approaches, including genomics and transcriptomics, as well as imaging and computational biology tools. All of this data is organized and made available to research teams to facilitate its use and enable the integration of different approaches.

Beyond data generation, this initiative also aims to foster collaboration between clinical and research teams. By facilitating access to samples and results, PancDEMIC helps to better coordinate research efforts and accelerate the emergence of new scientific hypotheses directly grounded in clinical observations.

PancDEMIC is part of a translational research initiative, with a clear goal of translating findings into clinical practice.

The data generated should help achieve several objectives, including identifying new biomarkers to better select treatments, offering patients more effective treatment combinations, anticipating resistance mechanisms, and, ultimately, improving patient care pathways. 

The program also serves as a foundation for the future development of large-scale integrated analyses, particularly using artificial intelligence methods, as the cohorts expand.

In the longer term, the infrastructure established within PancDEMIC is intended to serve as the foundation for future research projects, particularly by enabling the expansion of cohorts and the integration of new analytical technologies. It thus serves as a catalyst for sustainably structuring pancreatic cancer research at Gustave Roussy.

By building on this integrated organizational structure, PancDEMIC aims to make concrete progress in the understanding and management of pancreatic cancer.