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


RESULTS
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.


CONCLUSIONS
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.
Park
Min S
MS
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Ravi
Vinod
V
Araujo
Dejka M
DM
D000970:Antineoplastic Agents / Q000627:therapeutic use; D018323:Hemangioendothelioma, Epithelioid / Q000188:drug therapy / Q000503:physiopathology*; D006394:Hemangiosarcoma / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D054364:Solitary Fibrous Tumors / Q000188:drug therapy / Q000503:physiopathology*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor