Signal transduction targets in Kaposi's sarcoma.

PURPOSE OF REVIEW: AIDS-related Kaposi's sarcoma results from co-infection with HIV and Kaposi's sarcoma herpesvirus/human herpesvirus-8, which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of the condition. Recent discoveries regarding Kaposi's sarcoma herpesvirus/human herpesvirus-8 infection and its activation of signal transduction have led to a greater understanding into Kaposi's sarcoma pathogenesis and have identified potential targets for therapy.

RECENT FINDINGS: Kaposi's sarcoma is driven by Kaposi's sarcoma herpesvirus/human herpesvirus-8-specific pathways, which include viral G protein-coupled receptor, viral IL-6, and viral chemokine homologues. In addition, cellular growth/angiogenic pathways such as vascular endothelial growth factor, insulin growth factor, platelet-derived growth factor, angiopoietin and matrix metalloproteinases are 'pirated' by Kaposi's sarcoma herpesvirus/human herpesvirus-8. Recent findings show Kaposi's sarcoma herpesvirus/human herpesvirus-8 specific signaling pathways and pirated pathways to be important therapeutic targets.

SUMMARY: Numerous advances have been made recently that expand the understanding of Kaposi's sarcoma pathogenesis. These findings and recent clinical trials of targeted therapy for treatment are a prelude to a shift in the paradigm of how AIDS-related Kaposi's sarcoma is managed.