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PDAC incidence has been rising, with modifiable and non\u2010modifiable risk factors contributing to disease development. Chronic pancreatitis, diabetes mellitus, smoking, obesity, and familial predisposition have been implicated in PDAC pathogenesis. Early clinical manifestations are vague and insidious; therefore, PDAC is often diagnosed at an advanced stage, limiting curative treatment options. Efforts to improve early detection have focused on serum biomarkers (e.g., carbohydrate antigen 19\u20109), imaging modalities, and liquid biopsies. Endoscopic ultrasound and magnetic resonance imaging have demonstrated potential in identifying early\u2010stage disease in certain high\u2010risk populations. Surgical resection remains the only potentially curative option, but only 15%\u201320% of patients have resectable disease at diagnosis. Neoadjuvant chemotherapy has emerged as a promising strategy to improve resectability and survival outcomes. For patients with locally advanced or metastatic PDAC, combination chemotherapy regimens such as FOLFIRINOX (folinic acid, 5\u2010fluorouracil, irinotecan, and oxaliplatin), NALIRIFOX (5\u2010fluorouracil, oxaliplatin, liposomal irinotecan, and leucovorin), and combined gemcitabine\/nanoparticle albumen\u2010bound paclitaxel offer survival benefits, although toxicity remains a concern, especially for platinum\u2010based therapies. Several breakthroughs in molecular profiling have led to the development of targeted therapies, including sotorasib and olaparib. Immunotherapy has shown limited success in PDAC due to its immunosuppressive tumor microenvironment. However, novel combination approaches are under investigation, including quadruplet therapy, immune checkpoint inhibitors with oncolytic viruses, stromal\u2010targeting agents, and personalized neoantigen vaccines. Key priorities for future research include identifying reliable biomarkers for early detection, refining patient selection for targeted therapies, and developing innovative strategies to overcome treatment resistance.<\/jats:p>","DOI":"10.3322\/caac.70035","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T16:10:37Z","timestamp":1758298237000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Advances in pancreatic cancer early diagnosis, prevention, and treatment: The past, the present, and the future"],"prefix":"10.3322","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1655-6762","authenticated-orcid":false,"given":"Alessandro","family":"Mannucci","sequence":"first","affiliation":[{"name":"Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute at City of Hope  Monrovia California USA"},{"name":"Gastroenterology and 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