Inhibiting the VEGF-VEGFR pathway in angiosarcoma, epithelioid hemangioendothelioma, and hemangiopericytoma/solitary fibrous tumor

PURPOSE OF REVIEW: This review highlights the current body of knowledge regarding the role of the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in angiosarcoma, epithelioid hemangioendothelioma (EHE), and hemangiopericytoma/solitary fibrous tumor (HPC/SFT). Therapeutic agents that target this pathway are reviewed. RECENT FINDINGS: Several phase II trials in advanced soft tissue sarcoma patients have investigated the efficacy of bevacizumab, an anti-VEGF antibody, as well as sunitinib, sorafenib, and pazopanib, VEGFR tyrosine kinase inhibitors (TKIs). Although response rates and progression-free survival periods were generally low, several angiosarcoma, EHE, and HPC/SFT patients demonstrated response or durable disease stabilization on these therapies. Biological mechanisms underlying the activity of these agents in angiosarcoma, EHE, and HPC/SFT are poorly understood. Some angiosarcoma tumors, however, harbor specific activating mutations in VEGFR2, which may be effectively targeted by VEGFR TKIs. SUMMARY: Inhibition of the VEGF/VEGFR pathway may be a rational and effective therapy for certain patients with angiosarcoma, EHE, and HPC/SFT, but more studies are needed to confirm these findings and to identify which patients will benefit from these agents.