- Blood coagulation-(in)dependent protease activated receptor signaling in pancreatic cancer
- Award date
- 5 June 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
There is no doubt that pancreatic cancer is one of the most lethal diseases in general and current treatment options are limited.
The studies described in this thesis pinpoint Protease activated receptors (PARs) as key players in pancreatic cancer progression. Inhibition of PAR-1 may be clinical relevant for pancreatic cancer patients although the frequently observed bleeding complications with PAR-1 inhibitors should be kept in mind. The unexpected observed dual role of PAR-2 in the tumour microenvironment of pancreatic cancer strongly suggest that PAR-2 inhibition is not the first treatment of choice in pancreatic cancer patients. It would probably be more relevant to focus on the PAR-2-induced lymphangiogenesis inhibitor but this inhibitor still has to be identified. The dual role of PAR-2 may in part explain the small effect of anticoagulant treatment on overall survival in pancreatic cancer patients. Although blood coagulation seems to contribute to cancer progression, randomized clinical trials assessing the potential of anticoagulants in the treatment of cancer patients show only very (if any) limited benefit. As anticoagulants also inhibit TF/FVIIa- or FXa-induced PAR-2 signaling (with subsequent increased lymph node metastasis), the beneficial effect of inhibiting thrombin-dependent PAR-1 activation may be overshadowed.
- Research conducted at: Universiteit van Amsterdam
Thesis (complete) (Embargo up to and including 5 June 2019)
Chapter 4: Identity and specificity of a protease activated receptor-2-induced inhibitor of lymphangiogenesis in pancreatic cancer (Embargo up to and including 5 June 2019)
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