Pancreatic cancer

Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M. & Maitra, A. Pancreatic cancer: advances and challenges. Cell 186, 1729–1754 (2023).

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Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229–263 (2024).

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Grünwald, B. T. et al. Spatially confined sub-tumor microenvironments in pancreatic cancer. Cell 184, 5577–5592.e18 (2021). This study reveals that pancreatic TME heterogeneity is organized into distinct fibroblast-driven ‘subTMEs’ with defined immune and treatment-response patterns.

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Sherman, M. H. & Pasca di Magliano, M. Cancer-associated fibroblasts: lessons from pancreatic cancer. Annu. Rev. Cancer Biol. 7, 43–55 (2023).

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Steele, N. G. et al. Multimodal mapping of the tumor and peripheral blood immune landscape in human pancreatic cancer. Nat. Cancer 1, 1097–1112 (2020).

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Yousuf, S. et al. Spatially resolved multi-omics single-cell analyses inform mechanisms of immune dysfunction in pancreatic cancer. Gastroenterology 165, 891–908.e14 (2023).

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Isaji, S. et al. International consensus on definition and criteria of borderline resectable pancreatic ductal adenocarcinoma 2017. Pancreatology 18, 2–11 (2018). This international consensus defined pancreatic cancer resectability, shaping patient management and trial design.

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Conroy, T. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 364, 1817–1825 (2011). This trial shows that FOLFIRINOX results in significantly longer overall and progression-free survival than gemcitabine in patients with metastatic pancreatic cancer, although with higher toxicity.

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Von Hoff, D. D. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 369, 1691–1703 (2013). This study demonstrates that nab-paclitaxel plus gemcitabine is associated with longer survival and higher response rates than gemcitabine alone in metastatic pancreatic cancer, but with higher rates of neuropathy and myelosuppression.

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Wainberg, Z. A. et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet 402, 1272–1281 (2023).

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Rojas, L. A. et al. Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature 618, 144–150 (2023). This phase I trial shows that a personalized mRNA neoantigen vaccine combined with immunotherapy and chemotherapy induces strong neoantigen-specific T cell responses and is associated with delayed recurrence of resected pancreatic cancer.

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Sethna, Z. et al. RNA neoantigen vaccines prime long-lived CD8 + T cells in pancreatic cancer. Nature 639, 1042–1051 (2025). This follow-up study (to the study of Rojas et al. (2023)) corroborates that the personalized mRNA neoantigen vaccine autogene cevumeran induces durable CD8+T cells that persist for years and correlate with prolonged recurrence-free survival in pancreatic cancer.

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Pant, S. et al. Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial. Nat. Med. 30, 531–542 (2024).

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Wainberg, Z. A. et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results. Nat. Med. https://doi.org/10.1038/s41591-025-03876-4 (2025).

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Isermann, T., Sers, C., Der, C. J. & Papke, B. KRAS inhibitors: resistance drivers and combinatorial strategies. Trends Cancer 11, 91–116 (2025).

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Siegel, R. L., Kratzer, T. B., Wagle, N. S., Sung, H. & Jemal, A. Cancer statistics, 2026. CA Cancer J. Clin. 76, e70043 (2026).

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Klein, A. P. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nat. Rev. Gastroenterol. Hepatol. 18, 493–502 (2021).

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Cause for concern: the rising incidence of early-onset pancreatic cancer. Lancet Gastroenterol. Hepatol. 8, 287 (2023).

GBD 2017 Pancreatic Cancer Collaborators. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 4, 934–947 (2019). This work demonstrates that global incidence, deaths and disability-adjusted life-years from pancreatic cancer have more than doubled over the past three decades, mainly due to ageing and modifiable risks.

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Klein, A. P. Pancreatic cancer: a growing burden. Lancet Gastroenterol. Hepatol. 4, 895–896 (2019).

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Bosetti, C. et al. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann. Oncol. 23, 1880–1888 (2012).

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Genkinger, J. M. et al. Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol. Biomarkers Prev. 18, 765–776 (2009).

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Naudin, S. et al. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European prospective investigation into cancer and nutrition study. Int. J. Cancer 143, 801–812 (2018).

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Pang, Y. et al. Diabetes, plasma glucose and incidence of pancreatic cancer: a prospective study of 0.5 million Chinese adults and a meta-analysis of 22 cohort studies. Int. J. Cancer 140, 1781–1788 (2017).

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Chari, S. T. et al. Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology 129, 504–511 (2005).

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Duell, E. J. et al. Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann. Oncol. 23, 2964–2970 (2012).

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Chen, F. et al. Analysis of heritability and genetic architecture of pancreatic cancer: A PanC4 study. Cancer Epidemiol. Biomarkers Prev. 28, 1238–1245 (2019).

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Lichtenstein, P. et al. Environmental and heritable factors in the causation of cancer — analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).

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Hu, C. et al. Prevalence of pathogenic mutations in cancer predisposition genes among pancreatic cancer patients. Cancer Epidemiol. Biomarkers Prev. 25, 207–211 (2016).

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Shindo, K. et al. Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J. Clin. Oncol. 35, 3382–3390 (2017).

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