The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer

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X B Trinh1, W A A Tjalma, P B Vermeulen

  • 1Translational Cancer Research Group Antwerp, St Augustinus Hospital, Antwerp, Belgium.

British Journal of Cancer
|February 26, 2009
PubMed

Insights

Vascular endothelial growth factor (VEGF)-A signaling directly stimulates tumor cell AKT/mTOR pathways in ovarian cancer. This suggests VEGF inhibitors may target tumor cells, not just blood vessels, impacting treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Vascular endothelial growth factor (VEGF)-A inhibitors show significant efficacy and toxicity in recurrent epithelial ovarian cancer.
  • The VEGF/VEGFR pathway plays a crucial role in ovarian cancer progression.
  • The interplay between VEGF signaling and AKT/mTOR signaling in tumor cells is not fully understood.

Purpose of the Study:

  • To investigate the correlation between VEGF signaling and AKT/mTOR signaling in ovarian cancer.
  • To determine if VEGF signaling directly influences AKT/mTOR pathway activation in tumor cells.
  • To explore the clinical implications of this pathway interaction on patient outcomes.

Main Methods:

  • Utilized immunohistochemical staining on a tissue microarray of 86 clinical ovarian cancer samples.
  • Semi-quantified tumor cell staining for VEGF-A, pVEGFR2, pS6, and p4E-BP1.
  • Performed gene expression analysis on an independent dataset (N=24) to correlate RPS6 and VEGFR2 gene expression.

Main Results:

  • Found a significant correlation between VEGFR2 activation (pVEGFR2) and AKT/mTOR signaling (pS6) (R=0.29, P=0.002).
  • Observed an inverse correlation between RPS6 and VEGFR2 gene expression (R=-0.73, P<0.0001).
  • Activated VEGFR2/AKT/mTOR pathway correlated with increased ascites and reduced survival in serous ovarian cancer patients treated with cisplatin-taxane (P=0.04).

Conclusions:

  • VEGF-A signaling acts as a direct stimulator of the AKT/mTOR pathway within ovarian tumor cells.
  • VEGF inhibitors may possess a direct anti-tumor cell mechanism beyond anti-angiogenesis.
  • Targeting the VEGF/VEGFR-AKT/mTOR axis could offer novel therapeutic strategies for ovarian cancer.

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