mTOR inhibitors block Kaposi sarcoma growth by inhibiting essential autocrine growth factors and tumor angiogenesis.

Authors:
Sang-Hoon Sin
Sang-Hoon Sin
Dept. Microbiology & Immunology / University of North Carolina at Chapel Hill
Research Assistant Professor
KSHV
Chapel Hill, NC | United States

Cancer Res 2013 Apr 4;73(7):2235-46. Epub 2013 Feb 4.

Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Kaposi sarcoma originates from endothelial cells and it is one of the most overt angiogenic tumors. In Sub-Saharan Africa, where HIV and the Kaposi sarcoma-associated herpesvirus (KSHV) are endemic, Kaposi sarcoma is the most common cancer overall, but model systems for disease study are insufficient. Here, we report the development of a novel mouse model of Kaposi sarcoma, where KSHV is retained stably and tumors are elicited rapidly. Tumor growth was sensitive to specific allosteric inhibitors (rapamycin, CCI-779, and RAD001) of the pivotal cell growth regulator mTOR. Inhibition of tumor growth was durable up to 130 days and reversible. mTOR blockade reduced VEGF secretion and formation of tumor vasculature. Together, the results show that mTOR inhibitors exert a direct anti-Kaposi sarcoma effect by inhibiting angiogenesis and paracrine effectors, suggesting their application as a new treatment modality for Kaposi sarcoma and other cancers of endothelial origin.

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Source
http://dx.doi.org/10.1158/0008-5472.CAN-12-1851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618543PMC
April 2013
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