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A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies
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The role of tumor microenvironment in resistance to anti-angiogenic therapy

Shaolin Ma1,2, Sunila Pradeep1, Wei Hu1

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

F1000Research
|March 22, 2018
PubMed

Insights

Anti-angiogenic therapy improves progression-free survival but faces challenges with modest overall survival benefits and rapid drug resistance. Targeting the tumor microenvironment (TME) offers new strategies to overcome resistance in solid cancers.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Anti-angiogenic therapy shows promise in extending progression-free survival for solid tumors.
  • Limited overall survival benefits and the rapid development of drug resistance remain significant clinical hurdles.
  • The tumor microenvironment (TME) undergoes adaptive changes in response to anti-angiogenic treatments.

Purpose of the Study:

  • To review adaptive changes in the TME contributing to anti-angiogenic therapy resistance.
  • To explore novel therapeutic strategies targeting the TME to overcome resistance.
  • To synthesize findings from preclinical models and clinical studies on TME-mediated resistance.

Main Methods:

  • Comprehensive literature review of contemporary studies on anti-angiogenic therapy resistance.
  • Analysis of preclinical models investigating mechanisms of resistance.
  • Examination of dynamic changes in hypoxia signaling and stromal cells during treatment.

Main Results:

  • Identified multiple mechanisms of resistance emerging from adaptive TME changes.
  • Highlighted the role of hypoxia signaling and stromal cell dynamics in treatment failure.
  • Demonstrated the potential of TME-targeting strategies in preclinical settings.

Conclusions:

  • Adaptive changes in the TME are critical drivers of resistance to anti-angiogenic therapy.
  • Targeting the TME presents a promising avenue for enhancing therapeutic efficacy and overcoming resistance.
  • Further research into TME modulation is essential for improving patient outcomes in solid cancers.
Keywords:
MET signalinganti-angiogenic therapydrug resistancetumor microenvironment

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