7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          It has long been recognised that pancreatic cancer induces a hypercoagulable state that may lead to clinically apparent thrombosis. Although the relationship between pancreatic cancer and hypercoagulability is well described, the underlying pathological mechanism(s) and the interplay between these pathways remain a matter of intensive study. This review summarises existing data on epidemiology and pathogenesis of thrombotic complications in pancreatic cancer with a particular emphasis on novel pathophysiological pathways. Pancreatic cancer is characterised by high tumoural expression of tissue factor, activation of leukocytes with the release of neutrophil extracellular traps, the dissemination of tumour-derived microvesicles that promote hypercoagulability and increased platelet activation. Furthermore, other coagulation pathways probably contribute to these processes, such as those that involve heparanase, podoplanin and hypofibrinolysis. In the era in which heparin and its derivatives—the currently recommended therapy for cancer-associated thrombosis—might be superseded by direct oral anticoagulants, novel data from mouse models of cancer-associated thrombosis suggest the possibility of future personalised therapeutic approaches. In this dynamic era for cancer-associated thrombosis, the discovery of novel prothrombotic and proinflammatory mechanisms will potentially uncover pharmacological targets to prevent and treat thrombosis without adversely affecting haemostasis.

          Related collections

          Most cited references103

          • Record: found
          • Abstract: found
          • Article: not found

          Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases.

          Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics

            Summary Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based “liquid biopsies”.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Risk of Arterial Thromboembolism in Patients With Cancer

              The risk of arterial thromboembolism in patients with cancer is incompletely understood.
                Bookmark

                Author and article information

                Contributors
                nigel_key@med.unc.edu
                Journal
                Br J Cancer
                Br. J. Cancer
                British Journal of Cancer
                Nature Publishing Group UK (London )
                0007-0920
                1532-1827
                22 July 2019
                27 August 2019
                : 121
                : 5
                : 359-371
                Affiliations
                [1 ]ISNI 0000 0004 1757 3470, GRID grid.5608.b, Thrombotic and Haemorrhagic Disease Unit, Department of Medicine, , University of Padova, ; Padova, Italy
                [2 ]ISNI 0000000122483208, GRID grid.10698.36, Division of Haematology/Oncology, Department of Medicine, , University of North Carolina at Chapel Hill, ; Chapel Hill, NC USA
                Article
                510
                10.1038/s41416-019-0510-x
                6738049
                31327867
                5e161f3b-136f-492d-87e2-daa5fc269938
                © The Author(s), under exclusive licence to Cancer Research UK 2019

                This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

                History
                : 18 October 2018
                : 13 May 2019
                : 28 May 2019
                Categories
                Review Article
                Custom metadata
                © Cancer Research UK 2019

                Oncology & Radiotherapy
                tumour biomarkers,risk factors,outcomes research
                Oncology & Radiotherapy
                tumour biomarkers, risk factors, outcomes research

                Comments

                Comment on this article