Vegfrs in neoplastic angiogenesis and prospects for therapy of brain tumors

A. A. Korchagina, S. A. Shein, O. I. Gurina, V. P. Chekhonin

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Glioblastoma (GBM) is the most common type of primary brain cancer that characterized by poor prognosis due to the rapid progression, active angiogenesis, enhanced tumor cell invasion and the emergence of resistance toward conventional therapy. In this connection, nowadays, new approaches for selective inhibition of crucial steps in tumor progression are actively developing. The key feature of tumor growth and development is angiogenesis. VEGF and its receptor VEGFR2 play the pivotal role in regulation of tumor vessel formation. Therefore, VEGFR2, as the main receptor of VEGFs pro-angiogenic signal transducer, is a promising molecular target for anti-angiogenic therapy. There is evidence that inhibitors of VEGF and VEGFR2 reduce endothelial cell proliferation, migration and survival that lead to regression of vessel density and decrease vascular permeability, thereby slowing tumor growth. Currently, a number of VEGFR2 inhibitors are under clinical trials (ramucirumab, cediranib) and several were approved (sunitinib, sorafenib). Despite the promising results of preclinical studies, the efficacy of antiangiogenic drugs in the clinical practice is significantly lower, mainly, due to rapid adaptation of malignant cells that consists of alternative pro-angiogenic pathways activation, recruitment of endothelial progenitor cells from bone marrow and increasing of the invasive growth. Given the diversity of pro-angiogenic mechanisms, enhancement of the efficacy of tumor therapy could be achieved by specific inhibition of VEGFR2 functions that will be supplemented by other antiangiogenic drugs (anti-VEGF,-PlGF,-HIFlα). In addition, multitargeting therapy should focus on the combined inhibition of angiogenesis, invasion, metastasis, proliferation and survival of tumor cells.

Original languageEnglish (US)
Pages (from-to)104-114
Number of pages11
JournalVestnik Rossiiskoi Akademii Meditsinskikh Nauk
Issue number11
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Angiogenesis
  • Brain tumors
  • Inhibitors of angiogenesis
  • Site-directed therapy
  • VEGF
  • VEGFR2

ASJC Scopus subject areas

  • General Medicine

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