Investigational agents for treatment of AIDS-related Kaposi's sarcoma.
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.
Konstantinopoulos
Panagiotis A
PA
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Sullivan
Ryan J
RJ
Karamouzis
Michalis V
MV
Dezube
Bruce J
BJ
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D015507:Drugs, Investigational / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
D000998:Antiviral Agents; D015507:Drugs, Investigational