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Targeting vascular endothelial growth factor receptor in thyroid cancer: the intracellular and extracellular

Stephen M Keefe1, Marc A Cohen, Marcia S Brose

  • 1Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 28, 2010
PubMed

Insights

Targeted therapies for differentiated thyroid cancer (DTC) show promise by inhibiting key signaling pathways like B-Raf and Akt. Targeting vascular endothelial growth factor receptor-2 (VEGFR-2) may offer direct antitumor effects on DTC cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Differentiated thyroid cancer (DTC) pathogenesis involves aberrant B-Raf and Akt signaling.
  • DTC tumors are highly vascular and sensitive to vascular endothelial growth factor receptor-2 (VEGFR-2) inhibition.

Purpose of the Study:

  • To review key signaling pathways in thyroid cancer.
  • To discuss the implications of these pathways for targeted therapy.

Main Methods:

  • Review of current literature on DTC molecular pathophysiology.
  • Analysis of signaling pathways including B-Raf, Akt, and VEGFR-2.
  • Discussion of multikinase inhibitors targeting VEGFR-2.

Main Results:

  • B-Raf and Akt signaling are crucial in DTC tumorigenesis.
  • VEGFR-2 inhibition impacts both endothelial cells and potentially DTC cells directly.
  • Multikinase inhibitors like sorafenib, sunitinib, axitinib, and motesanib target VEGFR-2.

Conclusions:

  • Targeted therapies focusing on molecular pathways represent a promising approach for DTC treatment.
  • Understanding VEGFR-2's role on both tumor vasculature and cancer cells is key for effective therapy.
  • Further research into direct antitumor effects of VEGFR-2 inhibitors on DTC cells is warranted.

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