Targeting hemostasis-related moieties for tumor treatment

Abstract

Under normal conditions, the hemostatic system, that includes the involvement of the coagulation response and platelets, is anatomically and functionally inseparable from the vasculature. However, the hemostatic response always occurs in a wide range of tumors because of the high expression of coagulation initiator tissue factor (TF) in many tumor tissues, and due to the leakage of coagulation factors and platelets from the circulation system into the tumor interstitium through abnormal tumor vessels. Therefore, in addition to TF, these coagulation factors, platelets, the central moiety thrombin, the final product fibrin, and fibronectin, which is capable of stabilizing coagulation clots, are also abundant in tumors. These hemostasis-related moieties (HRMs), including TF, thrombin, fibrin, fibronectin, and platelets, are also closely associated with tumor progression, e.g., primary tumor growth and distal metastasis. The hemostatic response only occurs under pathological conditions, such as tumors, thrombosis, and atherosclerosis other than in normal tissues. The HRMs within tumors are also highly specific, establishing functional and therapeutic targets for tumor treatment. Therefore, strategies including active targeting to these moieties, modulation of HRMs deposited in the tumor microenvironment to improve tumor drug delivery, activation of prodrug by the coagulation complex formed during coagulation response, and direct inhibition of the tumor-promoting activity of HRMs could be designed for tumor therapy. In this review, we summarize various strategies that target HRMs for tumor treatment.

Keywords: Coagulation cascade; Fibrin; Fibronectin; Hemostasis-related moieties; Hemostatic response; Nanoparticles; Platelets; Thrombin; Tissue factor; Tumor drug delivery; Tumor microenvironment.