Related Experiment Video

Updated: Aug 9, 2025

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

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Exploiting metabolic vulnerabilities after anti-VEGF antibody therapy in ovarian cancer

Deanna Glassman1, Mark S Kim1, Meredith Spradlin2,3

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Unit 1362, 1515 Holcombe Blvd, Houston, TX 77030, USA.

Iscience
|February 24, 2023
PubMed

Insights

Targeting glutaminase (GLS) with a GLS inhibitor (GLSi) shows promise against ovarian cancer resistant to anti-vascular endothelial growth factor antibody (AVA) therapy. GLSi demonstrated antitumor effects and improved survival in preclinical models.

Area of Science:

  • Oncology
  • Metabolic Pathways
  • Drug Resistance

Background:

  • Anti-vascular endothelial growth factor antibody (AVA) therapy offers limited clinical benefit in ovarian cancer due to adaptive resistance.
  • Glutamine metabolism, regulated by glutaminase (GLS), is a key mechanism driving this resistance.

Purpose of the Study:

  • To investigate the efficacy of a glutaminase inhibitor (GLSi) in overcoming AVA resistance in ovarian cancer.
  • To evaluate GLSi as a therapeutic strategy in both combination and sequential treatment settings.

Main Methods:

  • In vitro studies assessed cytotoxicity of GLSi combined with bevacizumab in AVA-resistant ovarian cancer cells.
  • In vivo studies evaluated GLSi monotherapy and combination therapy in reducing tumor growth.
  • Hyperpolarized magnetic resonance spectroscopy (MRS) was used to assess metabolic changes in vivo.

Main Results:

  • GLSi in combination with bevacizumab showed significant cytotoxic effects on AVA-resistant cells in vitro.
  • GLSi monotherapy and combination therapy reduced tumor growth in vivo.
  • Sequential GLSi treatment post-AVA resistance decreased pyruvate-to-lactate conversion and improved survival.

Conclusions:

  • Glutaminase inhibition is a viable strategy to overcome adaptive resistance to AVA therapy in ovarian cancer.
  • GLSi demonstrates significant antitumor activity and survival benefits, justifying further clinical development.
Keywords:
CancerCellular physiologyOncology

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