Pancreatic ductal adenocarcinoma (PDA) is notoriously aggressive and hard to treat. The tumour microenvironment (TME) in PDA is highly dynamic and has been found to promote tumour progression, metastasis niche formation and therapeutic resistance. Intensive research of recent years has revealed an incredible heterogeneity and complexity of the different components of the TME, including cancer-associated fibroblasts, immune cells, extracellular matrix components, tumour vessels and nerves. It has been hypothesised that paracrine interactions between neoplastic epithelial cells and TME compartments may result in either tumour-promoting or tumour-restraining consequences. A better preclinical understanding of such complex and dynamic network systems is required to develop more powerful treatment strategies for patients. Scientific activity and the number of compelling findings has virtually exploded during recent years. Here, we provide an update of the most recent findings in this area and discuss their translational and clinical implications for basic scientists and clinicians alike.
- pancreatic fibrosis
- pancreatic cancer
- molecular carcinogenesis
- molecular oncology
- molecular mechanisms
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AN and CAB are shared first authors.
Contributors AN, CAB and TMG conceptualised the review, designed figures and tables and wrote several paragraphs of the manuscript, DÖ, ML, PM, MB, DAT wrote paragraphs of the manuscript, all authors critically revised the manuscript.
Funding This work was supported by the State of Hesse (LOEWE-Schwerpunkt ’Medical RNomics') and EU FP7 grant no. 602783 (large-scale integrated project ’CAM-PaC') and by funds from the DFG (KFO325). This paper reflects only the authors' views and the European Union is not liable for any use that may be made of the information contained therein. DAT is a distinguished scholar of the Lustgarten Foundation, Director of the Lustgarten Foundation-designated Laboratory of Pancreatic Cancer Research, and supported by the Cold Spring Harbor Laboratory Association, the V Foundation and the National Institutes of Health (NIH 5P30CA45508-29, 5P50CA101955-07, P20CA192996-03, 1U10CA180944-04, 1 U01CA224013-01, U01CA210240-01A1, 1R01CA188134-01, 1R01CA190092-04 and 5U10CA180944-05). DÖ received funding from the Swedish Research Council (2017-01531), and the Swedish Society of Medicine (SLS-691681 and SLS-786661), federal funds through the county council of Västerbotten (VLL-643451), the Cancer Research Foundation in Northern Sweden (AMP 17-877), The Swedish Foundation for International Cooperation in Research and Higher Education (PT2015-6432), the Knut and Alice Wallenberg Foundation and the Swedish Cancer Society (CAN 2017/332 and CAN 2017/827). PM received funding by the DFG (MI710/8-1; Mi710/10-1). AN received funding from the Deutsche Krebshilfe, Max Eder Research Group (110972 and 70113213).
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Commissioned; externally peer reviewed.
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