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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
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Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic therapy (Review)

Shigeru Kanda1, Yasuyoshi Miyata, Hiroshi Kanetake

  • 1National Hospital Organization, Nagasaki Hospital, Nagasaki, Japan. skanda-jua@umin.net

International Journal of Molecular Medicine
|June 6, 2007
PubMed

Insights

Antiangiogenic therapy targeting vascular endothelial growth factor (VEGF) has shown limited success. Targeting multiple proangiogenic pathways, including non-receptor tyrosine kinases, may improve cancer treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Antiangiogenic therapy, particularly vascular endothelial growth factor (VEGF) blockade, was expected to improve advanced cancer prognosis based on preclinical data.
  • Clinical trials of VEGF-targeted monotherapy have yielded disappointing results, suggesting limitations in this approach.

Purpose of the Study:

  • To review the role of non-receptor protein-tyrosine kinases in angiogenesis.
  • To discuss the potential of these kinases as novel therapeutic targets for antiangiogenic drug discovery in cancer.

Main Methods:

  • Review of existing literature on angiogenesis signaling pathways.
  • Analysis of the function of Src and Fes family kinases in endothelial cell responses to proangiogenic factors.

Main Results:

  • Angiogenesis is regulated by multiple proangiogenic factors beyond VEGF.
  • Non-receptor tyrosine kinases, including Src and Fes family members, are crucial for endothelial cell responses to various proangiogenic signals.
  • VEGF inhibition may lead to the selection of tumor cells utilizing alternative angiogenic pathways.

Conclusions:

  • Successful antiangiogenic therapy may necessitate simultaneous blockade of multiple signaling pathways.
  • Non-receptor tyrosine kinases represent promising new targets for developing more effective antiangiogenic cancer therapies.

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