The molecular evidence behind the adjunct use of anticoagulants and chemotherapy in pancreatic cancer treatment: A new role for anticoagulants?

Abstract

Pancreatic cancers include highly aggressive forms of neoplasms, with limited treatment options and high mortality rates. Recent studies have highlighted various molecular pathways underlying the dynamic modification of the coagulation cascade by pancreatic cancer cells, promoting the development of thromboembolic events and possibly contributing to tumor progression. As such, the use of anticoagulants as adjuncts to chemotherapy in the treatment of pancreatic neoplasms has become a topic of interest. A literature review of over 115 articles was conducted. The primary objective was to highlight the molecular pathways implicated in both pancreatic cancer and the coagulation cascade, as well as the influence of anti-coagulants on cancer related thromboembolic events and their potential use as anti-metastatic medications. Available data suggests significant reduction in thromboembolic events following adjunct treatment with anticoagulants, though an impact on overall survival remains poorly characterized. Several anti-coagulants were found to have prominent anti-metastatic effects, and in animal models improved overall survival and decreased tumor growth margins. Gene pathways such as Protease-Activated Receptor-1 (PAR-1) and Kirsten rat sarcoma viral oncogene (KRAS) are also heavily upregulated in the context of pancreatic cancer and further modified by anti-coagulant use. Further studies are needed to characterize the risks and efficacy of this treatment option in humans.