Background: Pancreatic adenocarcinoma is a relatively frequent cancer with an extremely poor prognosis. Until recently, the natural history of pancreatic adenocarcinoma has not been possible to study, but the identification of precursor lesions (pancreatic intraepithelial neoplasia, PanIN) has lead to a better understanding of the stepwise morphological and genetic alterations involved in the development of invasive adenocarcinoma.
Material And Methods: Relevant literature from the period of 1996-2005 was found by searching the Medline database, combining the terms "pancreas", "cancer", "PanIN" and "neoplasia". Principal original and review papers were extracted and used as background for a presentation of the PanIN cancer progression model.
Results And Interpretation: PanINs are established as designation of histological precursor lesions to pancreatic adenocarcinoma. PanIN grade I to III represent stepwise morphological alterations in the pancreatic ductal epithelium, from early neoplasia (PanIN I and II), via carcinoma in situ (PanIN III) to the development of invasive ductal adenocarcinoma. This model allows for the investigation of sequential molecular changes such as activation of oncogenes and inactivation of tumour suppressor genes. Increased knowledge about pancreatic carcinogenesis may pave the way for prevention strategies, early detection, and new treatment options, thus ultimately improving the prognosis of the patients.
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Gastroenterol Clin North Am
March 2025
Department of Surgery, University of Minnesota, 420 Delaware Street SE, MMC 195, Minneapolis, MN 55455, USA. Electronic address:
Surgical management of pancreas cancer is complex, including the timing of surgery, surgical approach, intraoperative techniques, and postoperative management, which are reviewed in detail in this manuscript. Ultimately, referral to a high-volume pancreatic surgeon or pancreatic surgery center is critical to ensuring appropriate short-term and long-term outcomes.
View Article and Find Full Text PDFGastroenterol Clin North Am
March 2025
Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, ST, Suite 7705, Los Angeles, CA 90048, USA. Electronic address:
Pancreatic cancer, often diagnosed at advanced stages, has poor survival rates. Effective screening aims to detect the disease early, improving outcomes. Current guidelines recommend screening high-risk groups, including those with a family history or genetic predispositions, using methods like endoscopic ultrasound and MRI.
View Article and Find Full Text PDFCell Rep Med
January 2025
State Key Laboratory of Systems Medicine for Cancer, Stem Cell Research Center, Ren Ji Hospital, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:
Pancreatic ductal adenocarcinoma (PDAC) relies heavily on glutamine (Gln) utilization to meet its metabolic and biosynthetic needs. How epigenetic regulators contribute to the metabolic flexibility and PDAC's response and adaptation to Gln scarcity in the tumor milieu remains largely unknown. Here, we elucidate that prolonged Gln restriction or treatment with the Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), leads to growth inhibition and ferroptosis program activation in PDAC.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
View Article and Find Full Text PDFAnn Surg Oncol
January 2025
Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives et Hépatiques, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.
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