Vascular endothelial growth factor in human colon cancer: Biology and therapeutic implications

Lee M. Ellis, Yutaka Takahashi, Wenbiao Liu, Raymond M. Shaheen

Research output: Contribution to journalArticlepeer-review

189 Scopus citations

Abstract

Tumor growth and metastasis are dependent on angiogenesis. Vascular endothelial growth factor (VEGF) plays an important role in the angiogenesis of numerous solid malignancies including colon cancer. Evidence from preclinical and clinical studies indicates VEGF is the predominant angiogenic factor in human colon cancer and is associated with formation of metastases and poor prognosis. Based on these results, it was hypothesized that inhibition of VEGF receptor activity could inhibit colon cancer liver metastasis. To test this hypothesis, the authors evaluated the ability of a small molecule inhibitor specific for the tyrosine kinase VEGF receptor Flk- 1/KDR (SU5416) or multiple tyrosine kinase receptors (SU6668) to inhibit tumor angiogenesis and metastasis in a model of colon cancer hepatic metastasis. Both SU5416 and SU6668 inhibited metastases, microvessel formation, and cell proliferation while increasing tumor cell and endothelial cell apoptosis. These results showed that targeting the VEGF receptor/ligand system is a rational approach to inhibiting tumor growth and prolonging survival.

Original languageEnglish (US)
Pages (from-to)11-15
Number of pages5
JournalOncologist
Volume5
Issue numberSUPPL. 1
DOIs
StatePublished - 2000

Keywords

  • Angiogenesis
  • Colon cancer
  • Metastasis
  • Receptors
  • Tyrosine kinase inhibitors
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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