A reduced incidence and regression of
Kaposi's sarcoma (KS) and other tumours has been reported in
Acquired Immune Deficiency Syndrome (
AIDS) patients treated with antiretroviral combination
therapies containing Human Immunodeficiency Virus (
HIV) protease inhibitors (PIs) such as
indinavir or
saquinavir. Indeed, evidence indicates that although PIs were designed to selectively inhibit the
HIV protease activity, they can interfere with several cellular pathways and can inhibit tumour growth. In particular, our recent results indicate that doses of
indinavir or
saquinavir similar to those employed to treat
AIDS patients can induce regression of experimental KS by directly blocking two fundamental steps of KS initiation and progression: new blood vessel formation (angiogenesis) and KS tumour cell invasion. This is because
indinavir or
saquinavir inhibit the activation of
matrix metalloproteinase-2 (MMP-2), a basement membrane-degrading
enzyme, which is required for the progression of most tumours. Based on these results, a multicentre clinical trial is now starting in Italy, which will assess PI effects on the progression of KS in HIV-uninfected individuals (classical KS).