Abstract
Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, characterized by late diagnosis, aggressive biology and limited therapeutic success. Advances in multiagent chemotherapy have improved outcomes across disease stages, whereas precision medicine approaches are reshaping treatment paradigms. Personalized RNA vaccines and oncogenic KRAS-directed agents represent emerging immunological and molecular frontiers. Multimodal treatment regimens and surgical innovations, including vessel-oriented and minimally invasive techniques, have enhanced complete resection rates and enabled conversion of initially unresectable locally advanced pancreatic cancer into resectable disease. Increasingly, multidisciplinary, biology-guided strategies define resectability and the sequence of systemic and local therapies. The tumour microenvironment’s complex stromal and immune ecology remains central to therapeutic resistance but also offers opportunities for rational combination therapy. Early detection and risk-adapted surveillance for high-risk individuals are advancing, as are artificial intelligence-assisted imaging and liquid biopsy approaches. Despite persistent challenges, the convergence of mechanistic insights, precision therapeutics and supportive care provides a framework for transforming pancreatic ductal adenocarcinoma from an inevitably lethal disease towards a better manageable condition.
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The authors gratefully acknowledge M. Gerberding for his editorial assistance.
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Introduction (C.W.M. and S.R.); Epidemiology (S.R. and A.P.K.); Mechanisms/pathophysiology (S.R., F.X.R., B.T.G., G.B., E.C., D.S. and M.A.); Diagnosis, screening and prevention (S.R., I.E., N.M., D.S. and M.K.); Management (C.W.M., S.R., E.M.O’R., T.C., J.T.S., V.P.B. and E.D.); Quality of life (C.W.M., S.R., E.M.O’R. and T.C.); Outlook (C.W.M., S.R. and M.J.P.); overview of Primer (C.W.M. and S.R.).
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A.P.K. has received grant support from the National Cancer Institute and support from the Lustgarten Foundation. J.T.S. has received honoraria as a consultant or for continuing medical education presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Immunocore, MSD Sharp Dohme, Novartis, Roche/Genentech and Servier; declares research funding to his institution from Abalos Therapeutics, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eisbach Bio, Oncolytics Biotech and Roche/Genentech; and holds ownership in FAPI Holding (<3%). M.J.P. acts as a consultant or ad hoc advisor to AstraZeneca, Merus, Merck, Moderna, Serna Bio, Revolution Medicines, Theriva Biologic and Boerhinger Ingelheim; is a member of the Steering Committee or Advisory Board for Astellas and RenovoRx; declares travel, accommodation and expenses support from Astellas, RenovoRx, Merus, Revolution Medicines; declares stock ownership in Perthera; and declares research funding to his institution from Tesaro, Arcus Bio, Ideaya, Repare Tx, Novartis, Pfizer, Merck, Tizonia, Biomed Valley Discoveries, Amgen, RenovoRx, Boerhinger Ingelheim, Astellas, Hutchinson Medipharma, Takeda, Actuate, MEI Pharma, Elevation Oncology, Recursion Pharma, Eli Lilly and Parabalis. E.D. declares research funding to his institution from Ipsen, Lutris and Relay; is a member of the advisory board for TME Therapeutics, Amgen, Abbvie, Agenus, Merck, Merus and Ipsen; acts a consultant to Lutris and Jazz Pharmaceuticals; and declares non-financial interests as a member of the Eastern Cooperative Oncology Group, on the NCI Pancreatic Task Force, and as a member of the PanCan Scientific Advisory Committee. E.M.O’R. declares research funding to her institution from Genentech/Roche, BioNTech, AstraZeneca, Arcus, Elicio Therapeutics, Parker Institute, NIH/NCI, Digestive Care, Break Through Cancer, Agenus, Amgen and Revolution Medicines; acts as a consultant or as a member of Data Safety Monitoring Boards (uncompensated) for Arcus, Amgen, AstraZeneca, Ability Pharma, Alligator BioSciences, Pfizer, Agenus, BioNTech, Ipsen, Ikena, Merck, Immuneering, Moma Therapeutics, Novartis, Astellas, BMS, Revolution Medicines, Regeneron and Tango Therapeutics; has received travel expenses from BioNTech and Arcus; declares other interests in relation to the American Association for Cancer Research, American Society of Clinical Oncology, Imedex, Research To Practice and Stand Up To Cancer (SU2C); and acknowledges NIH/NCI Cancer Center Support Grant/Core Grant P30 CA008748, NCI/NIH P50 CA257881-01A1. All other authors declare no competing interests.
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Roth, S., Apte, M., Balachandran, V.P. et al. Pancreatic cancer. Nat Rev Dis Primers 12, 23 (2026). https://doi.org/10.1038/s41572-026-00699-6
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DOI: https://doi.org/10.1038/s41572-026-00699-6
