Signal transduction targets in Kaposi's sarcoma.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Sullivan
Ryan
R
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Dezube
Bruce J
BJ
Koon
Henry B
HB
D002472:Cell Transformation, Viral; D015658:HIV Infections / Q000150:complications*; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D006801:Humans; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D015398:Signal Transduction