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In vivo intracellular signaling as a marker of antiangiogenic activity

C C Solorzano1, Y D Jung, C D Bucana

  • 1Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

Cancer Research
|October 5, 2001
PubMed

Insights

This study shows that blocking Erk and Akt signaling in tumor endothelial cells (ECs) with SU6668 can be a marker for effective antiangiogenic therapy. This approach may help monitor treatment success in liver metastases.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Endothelial cell (EC) signaling alterations can indicate effective antiangiogenic therapy.
  • SU6668 is a tyrosine kinase inhibitor with antiangiogenic properties.

Purpose of the Study:

  • To investigate the effect of SU6668 on tumor EC signaling in liver metastases in mice.
  • To evaluate Erk and Akt signaling pathways as potential biomarkers for antiangiogenic therapy efficacy.

Main Methods:

  • In vitro immunofluorescence to assess ECs pretreated with SU6668 and exposed to VEGF.
  • Double-fluorescence immunohistochemistry to analyze phosphorylated Erk and Akt in tumor ECs from mouse liver metastases.

Main Results:

  • SU6668 pretreatment decreased Erk and Akt phosphorylation in vitro.
  • Constitutive phosphorylation of Erk and Akt in ECs of untreated liver metastases was blocked by SU6668.
  • SU6668 effectively inhibited tumor EC signaling pathways in vivo.

Conclusions:

  • The activation status of Erk and Akt signaling pathways in tumor ECs can serve as a surrogate marker for antiangiogenic regimen effectiveness.
  • Monitoring EC signaling provides a potential method to assess therapeutic response to antiangiogenic drugs like SU6668.

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