The role of thrombin in the paradoxical interplay of cancer metastasis and the vascular system: A driving dynamic

Bayrak O., ALPER M., BAŞBINAR Y., BAYRAK S.

Biomedicine and Pharmacotherapy, vol.186, 2025 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Review
  • Volume: 186
  • Publication Date: 2025
  • Doi Number: 10.1016/j.biopha.2025.118031
  • Journal Name: Biomedicine and Pharmacotherapy
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Food Science & Technology Abstracts, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: Cancer, Drug repositioning, Oral anti-coagulants, Thrombin, Thrombosis
  • Dokuz Eylül University Affiliated: Yes

Abstract

The coagulation system plays a complex role in cancer therapy. Endothelial damage and tissue factor increased by chemotherapy initiate the coagulation cascade, producing active FXa and releasing thrombin. Thrombin triggers tumor growth and metastasis, leading to severe thromboembolic events in cancer patients. Direct thrombin inhibitors do not have the expected anti-metastatic effect as PAR-2 remains active and increases the risk of bleeding. Therefore, dual inhibition of thrombin by FXa inhibition and plasmin inhibition, which converts fibrin to fibrinogen, is targeted. Clinical studies show that the use of tranexamic acid in patients on NOAC therapy may be beneficial without increasing the risk of bleeding. This approach offers a promising strategy to provide an anti-metastatic effect in cancer treatment.