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Overcoming antiangiogenic resistance

James C Yao1, Alexandria Phan

  • 1Department of Gastrointestinal Medical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jyao@mdanderson.org

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|August 11, 2011
PubMed

Insights

Anti-angiogenesis drugs offer limited disease control and survival benefits. Therapeutic hypoxia can trigger resistance pathways, necessitating strategies to overcome this evasion for improved patient outcomes.

Area of Science:

  • Oncology
  • Vascular Biology
  • Drug Resistance

Background:

  • Angiogenesis inhibitors are crucial cancer therapies.
  • Current treatments show transient efficacy and modest survival gains.
  • Therapeutic hypoxia is a key mechanism of treatment resistance.

Purpose of the Study:

  • To investigate the mechanisms of evasive resistance to anti-angiogenesis therapy.
  • To identify pathways upregulated by hypoxic stress during treatment.
  • To explore strategies for overcoming treatment resistance to improve outcomes.

Main Methods:

  • Analysis of molecular pathways involved in angiogenesis and invasion.
  • Assessment of hypoxic stress markers in preclinical models.
  • Evaluation of combination therapies targeting resistance mechanisms.

Main Results:

  • Successful anti-angiogenesis therapy induces significant hypoxic stress.
  • Hypoxia upregulates pro-angiogenic and invasive pathways, leading to resistance.
  • Targeting these resistance pathways shows potential for enhanced therapeutic effect.

Conclusions:

  • Evasive resistance is a major limitation of current anti-angiogenesis drugs.
  • Understanding hypoxia-induced pathways is critical for overcoming resistance.
  • Developing strategies to counteract evasive resistance may significantly improve cancer treatment efficacy and patient survival.

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