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Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
07:59

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1

Published on: December 5, 2020

Targeting the insulin growth factor and the vascular endothelial growth factor pathways in ovarian cancer

Minghai Shao1, Stacy Hollar, Daphne Chambliss

  • 1Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

Molecular Cancer Therapeutics
|June 16, 2012
PubMed

Insights

Bevacizumab therapy for ovarian cancer can be overcome by insulin-like growth factor 1 (IGF-1) activation. Combining anti-VEGF and anti-IGF-1 therapies enhances ovarian cancer xenograft apoptosis and tumor growth inhibition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Antiangiogenic therapy, particularly with bevacizumab, shows promise for ovarian cancer but often yields transient clinical benefits.
  • Tumor resistance mechanisms can emerge during anti-VEGF treatment, necessitating the identification of alternative angiogenic pathways.

Purpose of the Study:

  • To identify and target alternative angiogenic pathways upregulated during bevacizumab treatment in ovarian cancer xenografts.
  • To evaluate the efficacy of dual blockade of VEGF and IGF-1 signaling in ovarian cancer models.

Main Methods:

  • Angiogenesis-focused gene expression arrays and reverse transcription-PCR were used to identify upregulated genes in bevacizumab-treated ovarian xenografts.
  • In vivo studies utilized bevacizumab and cixutumumab (anti-IGF-1 antibody) to assess combination therapy effects.
  • Immunohistochemistry and TUNEL assays were employed to measure tumor cell apoptosis, proliferation, and angiogenesis.

Main Results:

  • Insulin-like growth factor 1 (IGF-1) was found upregulated in tumor and stromal cells following bevacizumab treatment in ovarian xenografts.
  • Combination therapy with bevacizumab and cixutumumab significantly increased tumor cell apoptosis compared to monotherapy.
  • Dual blockade resulted in enhanced inhibition of tumor growth, blocked angiogenesis, and reduced cell proliferation.

Conclusions:

  • IGF-1 activation is a key adaptive escape mechanism during anti-VEGF therapy in ovarian cancer.
  • Combining bevacizumab with IGF-1 blockade offers a rational strategy to overcome treatment resistance and enhance antitumor activity.
  • This study supports the development of combination regimens for improved ovarian cancer treatment outcomes.

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