Targeting clotting proteins in cancer therapy – progress and challenges

• Progress in the understanding of TF activation and signaling provides new perspectives for coagulation contributions to cancer-associated thrombosis and tumor progression
• Extravascular coagulation signaling plays novel roles in stem cell niches and the tumor microenvironment with implications for anticoagulant therapy in cancer

ABSTRACTCancer-associated thrombosis remains a significant complication in the clinical management of cancer and interactions of the hemostatic system with cancer biology continue to be elucidated. Here, we review recent progress in our understanding of tissue factor (TF) regulation and procoagulant activation, TF signaling in cancer and immune cells, and the expanding roles of the coagulation system in stem cell niches and the tumor microenvironment. The extravascular functions of coagulant and anti-coagulant pathways have significant implications not only for tumor progression, but also for the selection of appropriate target specific anticoagulants in the therapy of cancer patients.