mTOR Inhibitors Block Kaposi Sarcoma Growth by Inhibiting Essential Autocrine Growth Factors and Tumor Angiogenesis

作者：Roy Debasmita; Sin Sang Hoon; Lucas Amy; Venkataramanan Raman; Wang Ling; Eason Anthony; Chavakula Veenadhari; Hilton Isaac B; Tamburro Kristen M; Damania Blossom; Dittmer Dirk P^*

来源：Cancer Research, 2013, 73(7): 2235-2246.

DOI：10.1158/0008-5472.CAN-12-1851

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. Cancer Res; 73(7); 2235-46.

• 出版日期2013-4-1