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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

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Published on: December 9, 2015

Understanding and targeting resistance to anti-angiogenic therapies

Jeffrey M Clarke1, Herbert I Hurwitz

  • 1Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.

Journal of Gastrointestinal Oncology
|September 3, 2013
PubMed

Insights

Anti-angiogenic therapies show limited success due to resistance mechanisms. Combining agents targeting alternative pathways may improve tumor control and patient outcomes by optimizing angiogenesis inhibition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor angiogenesis therapies are widely used but face challenges with patient response and modest, transient effects.
  • Mechanisms of resistance to anti-angiogenic therapies include VEGF-axis dependent alterations, non-VEGF pathways, and stromal cell interactions.

Purpose of the Study:

  • To review preclinical evidence for mechanisms of angiogenic resistance.
  • To provide an overview of novel therapeutic strategies targeting these resistance pathways.

Main Methods:

  • Literature review of preclinical studies on anti-angiogenic therapy resistance.
  • Analysis of VEGF-axis dependent and independent resistance mechanisms.
  • Exploration of complementary therapeutic combinations.

Main Results:

  • Resistance to anti-angiogenic therapies is multifactorial, involving both VEGF-dependent and independent pathways.
  • Stromal cell interactions play a significant role in mediating resistance.
  • Preclinical data supports the potential of combination therapies to overcome resistance.

Conclusions:

  • Understanding resistance mechanisms is crucial for improving anti-angiogenic therapy efficacy.
  • Targeting alternative pathways and stromal interactions offers promising strategies for combination therapy.
  • Novel therapeutic approaches are needed to enhance clinical benefit and overcome resistance in cancer patients.
Keywords:
CancerVEGFangiogenesiscolorectal cancerresistancevascular endothelial growth factor

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