Anticoagulants in cancer treatment: malignancy as a solid phase coagulopathy.
The purpose of this review is to demonstrate the potential for development of coagulation-reactive drugs for experimental cancer treatment. Improved cancer outcome has been reported in several tumor types with drugs that interfere with thrombin-generating or urokinase-initiated pathways expressed by tumor cells. These pathways participate in the response to injury and their inappropriate expression by malignant cells supports tumor growth. A proposed classification of tumor types based on the differential occurrence of these pathways may account for variation in drug responsiveness and guide clinical trial design. Among drugs available for testing, aprotinin and low molecular weight heparin have particular appeal. The former blocks a pathway of tumor cell growth, invasion and metastasis while the latter blocks growth factor activity, angiogenesis, and other tumor growth mechanisms as well as coagulation activation. Conceiving of malignancy as a solid phase coagulopathy may facilitate development of effective but non-toxic cancer treatments and encourage inquiry into the putative 'injury' responsible for both coagulation activation and carcinogenesis.
Research Service (151), VA Medical Center, White River Junction, VT 05009, USA. leo.r.zacharski@dartmouth.edu
Leo R
LR
Zacharski
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000150:complications; D006801:Humans; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D020246:Venous Thrombosis / Q000150:complications
D000925:Anticoagulants