Protease inhibitors kill tumors

Patients infected with HIV-1 undergoing protease inhibitor (PI) treatment have a reduced incidence or regression of Kaposi sarcoma (KS), but the molecular mechanism of this response remains unclear. In March Nature Medicine, Cecilia Sgadari and colleagues from Istituto Superiore di Sanità, Rome, Italy, show that HIV protease inhibitors promote regression of KS because they are potent anti-angiogenic molecules.

Sgadari et al. used in vitro and in vivo models of angiogenesis, KS-lesion formation and tumor growth. They found that systemic administration of the PIs indinavir or saquinavir to nude mice had direct anti-angiogenic, anti-KS and anti-tumor activity at concentrations present in the plasma of treated individuals. In addition, the PIs blocked basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF)-induced angiogenesis in a chorioallantoic membrane assay, with a potency similar to the classic anticancer drug paclitaxel (Taxol) (Nat Med 2002, 8:225-232).

"These results indicate that PIs are promising anti-angiogenic ...