From classical approaches to artificial intelligence, old and new tools for PDAC risk stratification and prediction.

Journal: Seminars in cancer biology
PMID:

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal malignancies, characterized by late-stage diagnosis and limited therapeutic options. Risk stratification has traditionally been performed using epidemiological studies and genetic analyses, through which key risk factors, including smoking, diabetes, chronic pancreatitis, and inherited predispositions, have been identified. However, the multifactorial nature of PDAC has often been insufficiently addressed by these methods, leading to limited precision in individualized risk assessments. Advances in artificial intelligence (AI) have been proposed as a transformative approach, allowing the integration of diverse datasets-spanning genetic, clinical, lifestyle, and imaging data into dynamic models capable of uncovering novel interactions and risk profiles. In this review, the evolution of PDAC risk stratification is explored, with classical epidemiological frameworks compared to AI-driven methodologies. Genetic insights, including genome-wide association studies and polygenic risk scores, are discussed, alongside AI models such as machine learning, radiomics, and deep learning. Strengths and limitations of these approaches are evaluated, with challenges in clinical translation, such as data scarcity, model interpretability, and external validation, addressed. Finally, future directions are proposed for combining classical and AI-driven methodologies to develop scalable, personalized predictive tools for PDAC, with the goal of improving early detection and patient outcomes.

Authors

  • Riccardo Farinella
    Department of Biology, University of Pisa, Pisa, Italy.
  • Alessio Felici
    Department of Biology, University of Pisa, Via Luca Ghini, 13 - 56126, Pisa, Italy. Electronic address: alessio.felici@phd.unipi.it.
  • Giulia Peduzzi
    Department of Biology, University of Pisa, Via Luca Ghini, 13 - 56126, Pisa, Italy. Electronic address: giulia.peduzzi@biologia.unipi.it.
  • Sabrina Gloria Giulia Testoni
    Division of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Policlinico San Donato, Vita-Salute San Raffaele University, Milan, Italy.
  • Eithne Costello
    Liverpool Experimental Cancer Medicine Centre, University of Liverpool, Liverpool, United Kingdom. Electronic address: ecostell@liverpool.ac.uk.
  • Paolo Aretini
    Fondazione Pisana per la Scienza ONLUS, Italy.
  • Ricardo Blazquez-Encinas
    Department of Cell Biology, Physiology and Immunology, University of Cordoba / Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain.
  • Elif Öz
    Department of Biostatistics and Bioinformatics, Acibadem Mehmet Ali Aydinlar University, Turkiye.
  • Aldo Pastore
    Fondazione Pisana per la Scienza, Scuola Normale Superiore di Pisa, Italy.
  • Matteo Tacelli
    Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational & Clinical Research Center, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy. Electronic address: tacelli.matteo@hsr.it.
  • Burçak Otlu
    Department of Health Informatics, Graduate School of Informatics, Middle East Technical University, Ankara, Turkey.
  • Daniele Campa
    Department of Biology, University of Pisa, Via Luca Ghini, 13 - 56126, Pisa, Italy. Electronic address: daniele.campa@unipi.it.
  • Manuel Gentiluomo
    Department of Biology, University of Pisa, Italy.