Abstract
AIDS-related Kaposi’s sarcoma (KS) is a neoplasm that results from the co-infection of HIV and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8). Targeting HIV with highly active antiretroviral therapy has attenuated the natural history of this disease. Recent discoveries have elucidated the role of multiple signaling pathways in the pathogenesis of AIDS-related KS. In particular, KSHV/HHV8-specific gene products, including a G-protein-coupled receptor (vGPCR) and a homolog of human IL-6 (vIL-6), have been implicated in the development of tumorigenesis and angiogenesis. In addition, KSHV/HHV8 can modulate cellular growth and angiogenic pathways to augment malignant transformation and potentiate growth. This article discusses the main signaling pathways that are implicated in the pathogenesis of AIDS-related KS, reviews recently completed clinical trials and anticipates the future direction of molecularly targeted agents in this disease.
Acknowledgements
The authors thank HB Koon, MD for critical review of this manuscript, and are grateful to J Bell and J Hayward of Media Services for assistance with Figure 1.
Notes
*Targets for which inhibitors have been tested or are being tested as therapy against KS. bFGF: Basic fibroblast growth factor; HHV: Human herpesvirus; HIF: Hypoxia-inducible factor; IGF: Insulin-like growth factor; KS: Kaposi’s sarcoma; KSHV: KS herpesvirus; MMP: Matrix metalloprotease; PDGF: Platelet-derived growth factor; SCF: Stem cell factor; vCCl: Viral CC-class chemokine; VEGF: Vascular endothelial growth factor; vGPCR: A G-protein-coupled receptor encoded by KSHV; vIL: Viral IL encoded by KSHV.