Abstract
Late diagnosis of pancreatic ductal adenocarcinoma (pancreatic cancer) and the limited response to current treatments results in an exceptionally poor prognosis. Advances in our understanding of the molecular events underpinning pancreatic cancer development and metastasis offer the hope of tangible benefits for patients. In-depth mutational analyses have shed light on the genetic abnormalities in pancreatic cancer, providing potential treatment targets. New biological studies in patients and in mouse models have advanced our knowledge of the timing of metastasis of pancreatic cancer, highlighting new directions for the way in which patients are treated. Furthermore, our increasing understanding of the molecular events in tumorigenesis is leading to the identification of biomarkers that enable us to predict response to treatment. A major drawback, however, is the general lack of an adequate systematic approach to advancing the use of biomarkers in cancer drug development, highlighted in a Cancer Biomarkers Collaborative consensus report. In this Review, we summarize the latest insights into the biology of pancreatic cancer, and their repercussions for treatment. We provide an overview of current treatments and, finally, we discuss novel therapeutic approaches, including the role of biomarkers in therapy for pancreatic cancer.
Key Points
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Pancreatic cancer is genetically a heterogeneous disease that has a limited response to treatment
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No accepted way of predicting which patients will respond to treatment currently exists
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Research is building on advances in our understanding of the molecular pathogenesis of pancreatic cancer to identify more sensitive and robust biomarkers
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Mouse models and translational studies have further elucidated the timing of metastasis and the therapeutic window in pancreatic cancer
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The intense stromal response in pancreatic cancer offers one explanation for therapeutic failure and merits further biomarker development
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Costello, E., Greenhalf, W. & Neoptolemos, J. New biomarkers and targets in pancreatic cancer and their application to treatment. Nat Rev Gastroenterol Hepatol 9, 435–444 (2012). https://doi.org/10.1038/nrgastro.2012.119
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DOI: https://doi.org/10.1038/nrgastro.2012.119
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