Thursday, September 29, 2011
Tissue factor-activated coagulation cascade. The tissue factor (TF)-induced coagulation cascade is
constantly activated in the tumor microenvironment because TF is overexpressed
on tumor cell surfaces and inactive coagulation factors, including factors V
(FV) and X (FX) (light blue circles), move out of the excessively permeable
coagulation cascade is activated when TF forms a complex with factor VII
(FVII), which is activated to FVIIa. The complex then induces a series of
reactions that activate coagulation factor enzymes (dark blue circles),
ultimately converting prothrombin to thrombin and fibrinogen to fibrin,
activating blood clotting.
al. designed doxorubicin prodrugs that exploit the tumor-specific TF
activation. The prodrugs are separately hydrolyzed by the TF:FVIIa complex and
by thrombin in the tumor microenvironment, but not in the microenvironment of
healthy tissue. This results in accumulation of doxorubicin in the tumor.