Abstract
Pancreatic cancer is a major cause of cancer-associated mortality, with a dismal overall prognosis that has remained virtually unchanged for many decades. Currently, prevention or early diagnosis at a curable stage is exceedingly difficult; patients rarely exhibit symptoms and tumours do not display sensitive and specific markers to aid detection. Pancreatic cancers also have few prevalent genetic mutations; the most commonly mutated genes are KRAS, CDKN2A (encoding p16), TP53 and SMAD4 — none of which are currently druggable. Indeed, therapeutic options are limited and progress in drug development is impeded because most pancreatic cancers are complex at the genomic, epigenetic and metabolic levels, with multiple activated pathways and crosstalk evident. Furthermore, the multilayered interplay between neoplastic and stromal cells in the tumour microenvironment challenges medical treatment. Fewer than 20% of patients have surgically resectable disease; however, neoadjuvant therapies might shift tumours towards resectability. Although newer drug combinations and multimodal regimens in this setting, as well as the adjuvant setting, appreciably extend survival, ∼80% of patients will relapse after surgery and ultimately die of their disease. Thus, consideration of quality of life and overall survival is important. In this Primer, we summarize the current understanding of the salient pathophysiological, molecular, translational and clinical aspects of this disease. In addition, we present an outline of potential future directions for pancreatic cancer research and patient management.
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Acknowledgements
This work was partially supported by the COST action BM1204 “EUPancreas: An integrated European platform for pancreas cancer research: from basic science to clinical and public health interventions for a rare disease” (eupancreas.com) to J.K., C.L.V. and J.P.N. This work was also partially supported by National Cancer Institute (NCI) grants CA-075059 (to M.K.) and CA62924 (to R.H.H.); a grant from the Cancer Council New South Wales RG 13–01 (to M.A.); a grant from the Italian Foundation for Research on Cancer (to C.L.V.); a grant from the Lustgarten Foundation (to D.A.T.); a grant from the US Department of Defense (W81XWH-13-PRCRP-IA) (to D.A.T.); NIH grants 5P30CA45508-26, 5P50CA101955-07, 1U10CA180944-01, 5U01CA168409-3 and 1R01CA190092-01 (to D.A.T). R.E.N. is funded by a National Health and Medical Research Council (Australia) senior research fellowship. J.P.N. is The Owen and Ellen Evans Chair of Surgery, University of Liverpool, UK, and is a NIH Research (NIHR) Senior Investigator.
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Introduction (J.K.); Epidemiology (C.L.V. and R.E.N.); Mechanisms/pathophysiology (M.K., A.V.B., M.A., J.K. and D.A.T.); Diagnosis, screening and prevention (M.K., R.H.H. and R.E.N.); Management (M.A., J.K., J.P.N. and M.T.); Quality of life (C.D.J.); Outlook (J.K. and A.V.B.); Overview of the Primer (J.K.). All authors read and approved the final version of the manuscript.
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R.H.H. receives royalty payments from Myriad Genetics for the PALB2 invention in a relationship that is managed by Johns Hopkins University. The remaining authors declare no competing interests.
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Kleeff, J., Korc, M., Apte, M. et al. Pancreatic cancer. Nat Rev Dis Primers 2, 16022 (2016). https://doi.org/10.1038/nrdp.2016.22
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DOI: https://doi.org/10.1038/nrdp.2016.22
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