Rationale for clinical trials of coagulation: reactive drugs in hepatocellular carcinoma.
Evidence for the regulation of cancer growth by components of the blood coagulation mechanism provides abundant opportunity for the development of novel hypotheses for the experimental treatment of malignancy. Information available on the heterogeneity in mechanisms of interaction between various cancer cell types, and procoagulant and fibrinolytic pathways, platelets, glycosaminoglycan-regulated growth factors and cell-adhesion molecules indicates that insightful clinical trial design may allow targeting of individual cancer cell types with agents capable of intercepting mechanisms of growth control that are relevant to specific tumor types. This paper reviews the evidence that the common anticoagulant, heparin, inhibits hepatocellular carcinoma cell proliferation and hepatocellular carcinoma tumor dissemination in experimental animals. Clinical trials of heparin performed to date have shown increased tumor response rates and survival in other tumor types. Expression of urokinase-type plasminogen activator by hepatocellular carcinoma cells enhances tumor cell proliferation, motility, invasiveness and metastatic dissemination. Inhibition of the urokinase-type plasminogen activator/plasmin system by protease inhibitors such as aprotinin (Trasylol, Bayer) have shown improvement in the clinical course of certain tumor types. These data suggest that drugs that are well-known in the field of vascular medicine may find a role in the treatment of hepatocellular carcinoma, a common tumor type that has resisted containment by other means.
Zacharski
Leo R
LR
Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, VA Medical Center, 215 North Main Street, White River Junction, Vermont 05009, USA. leo.r.zacharski@dartmouth.edu
Hommann
Merten
M
Kaufmann
Roland
R
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D006493:Heparin; D014568:Urokinase-Type Plasminogen Activator