VEGF in Tumor Progression and Targeted Therapy
Vladimir P. Chekhonin, Sergey A. Shein, Anna A. Korchagina and Olga I. Gurina
Affiliation: 119991, Kropotkinsky Per. 23, Russia, Moscow.
Progression of solid tumors depends on vascularization and angiogenesis in a malignant tissue. Among a whole
range of proangiogenic factors, a vascular endothelial growth factor A (VEGF-A) plays a key role. Blockade of VEGF
may lead to regression of vascular network and inhibition of a tumor growth. In the present time, bevacizumab has been
introduced into wide clinical practice in therapy of breast cancer, colorectal cancer and recurrent high-grade gliomas
(HGGs). Coadministration of antiangiogenic therapy with irinotecan may increase probability of the response to the treatment
and prolong progression-free survival rate (PFS). Moreover, bevacizumab is well tolerated and significantly improves
patient’s quality of life. However, in the case of brain tumors, the efficiency of such an approach is controversial. The
antiangiogenic therapy can slightly delay tumor growth and does not lead to complete recovery. In addition, it contributes
to enhanced tumor cell invasion into the normal brain. The mechanisms of resistance include activation of alternative
proangiogenic signaling pathways, of an invasive population of tumor cells, metabolic change toward glycolysis and
recruitment of myeloid bone marrow-derived cells to tumors. Obviously, that anti-VEGF therapy as monotherapy was not
effective against HGGs. To enhance the antitumor treatment efficacy, it is necessary to develop a multi-target strategy to
inhibit critical processes in malignancy progression such as angiogenesis, invasion, autophagy, metastatic spread,
recruitment of bone marrow-derived endothelial cells and tumor stem-like cells. In addition, anti-VEGF antibodies have
shown a promising result as a tumor-targeting vector for delivery therapeutic and diagnostic drugs in brain tumors.
Keywords: Antiangiogenic therapy, bevacizumab, cell invasion, glioma, target therapy, tumor resistance, VEGF.
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