Perspectives et limites de l’innovation thérapeutique dans le cancer du pancréas

Details

Supervisors

Jacquemin, Patrick

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences pharmaceutiques, à finalité spécialisée

Abstract

enPancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with survival outcomes that have changed only marginally over the past decades. Accounting for approximately 90% of pancreatic cancers, PDAC is associated with a five-year survival rate below 10%, despite extensive clinical development and major advances in the understanding of its molecular and biological features. This work examines the reasons underlying the limited therapeutic progress in PDAC and evaluates the actual contribution of current and emerging pharmacological strategies. Therapeutic failure in PDAC reflects less a lack of molecular targets or innovative concepts than a persistent mismatch between tumor biology and therapeutic development. Key biological constraints (including extensive desmoplasia, early establishment of an immunosuppressive tumor microenvironment, and the central role of KRAS-driven signaling) continue to limit treatment efficacy. Through a critical review of international guidelines, clinical trial data, and emerging therapeutic approaches, this work assesses the clinical relevance of standard treatments and ongoing innovations, including targeted therapies, immunotherapy-based strategies, combination regimens, nanomedicine, PROTACs, and artificial intelligence-supported approaches. Overall, the available evidence shows that the expansion of therapeutic strategies has not translated into sustained and clinically meaningful improvements in PDAC outcomes. Reported benefits remain modest, short-lived, and restricted to selected patient subsets. These observations highlight persistent translational limitations, related in particular to insufficiently predictive preclinical models, incomplete integration of tumor heterogeneity, and clinical trial designs that do not adequately capture the biological and clinical complexity of PDAC. This work concludes that further progress in PDAC is unlikely to result from the incremental addition of new agents alone. Meaningful therapeutic advances will require improved biological alignment between preclinical models, molecular stratification, and clinical trial methodology, with greater emphasis on disease-specific constraints. Without such adjustments, therapeutic innovation in PDAC is expected to remain limited in its clinical impact.