Targeting angiogenesis in cancer therapy: Moving beyond vascular endothelial growth factor

Yujie Zhao, Alex Adjei

Research output: Contribution to journalArticle

204 Scopus citations

Abstract

Angiogenesis, or the formation of new capillary blood vessels, occurs primarily during human development and reproduction; however, aberrant regulation of angiogenesis is also a fundamental process found in several pathologic conditions, including cancer. As a process required for invasion and metastasis, tumor angiogenesis constitutes an important point of control of cancer progression. Although not yet completely understood, the complex process of tumor angiogenesis involves highly regulated orchestration of multiple signaling pathways. The proangiogenic signaling molecule vascular endothelial growth factor (VEGF) and its cognate receptor (VEGF receptor 2 [VEGFR-2]) play a central role in angiogenesis and often are highly expressed in human cancers, and initial clinical efforts to develop antiangiogenic treatments focused largely on inhibiting VEGF/VEGFR signaling. Such approaches, however, often lead to transient responses and further diseaseprogression because angiogenesis is regulated by multiple pathways that are able to compensate for each other when single pathways are inhibited. The platelet-derived growth factor (PDGF) and PDGF receptor (PDGFR) and fibroblast growth factor (FGF) and FGF receptor (FGFR) pathways, for example, provide potential escape mechanisms from anti-VEGF/VEGFR therapy that could facilitate resumption of tumor growth. Accordingly, more recent treatments have focused on inhibiting multiple signaling pathways simultaneously. This comprehensive review discusses the limitations of inhibiting VEGF signaling alone as an antiangiogenic strategy, the importance of other angiogenic pathways including PDGF/ PDGFR and FGF/FGFR, and the novel current and emerging agents that target multiple angiogenic pathways for the treatment of advanced solid tumors.

Original languageEnglish (US)
Pages (from-to)660-673
Number of pages14
JournalOncologist
Volume20
Issue number6
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Keywords

  • Angiogenesis inhibitors
  • Antibodies, monoclonal, humanized
  • Fibroblast growth factor
  • Molecular targeted therapy
  • Platelet-derived growth factor
  • Receptors
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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