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Combining antiangiogenics to overcome resistance: rationale and clinical experience

Victor Moreno Garcia1, Bristi Basu, L Rhoda Molife

  • 1Division of Clinical Sciences, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, Surrey, United Kingdom. victor.moreno@salud.madrid.org

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|May 2, 2012
PubMed

Insights

Combining antiangiogenic therapies shows promise for overcoming resistance in metastatic cancers. However, managing overlapping toxicities remains a critical challenge for clinical application.

Area of Science:

  • Oncology
  • Cancer Research
  • Pharmacology

Background:

  • Antiangiogenic therapies are established in oncology but face disappointing trial results, especially in adjuvant settings.
  • Resistance to antiangiogenic agents in metastatic disease often involves alternative angiogenic pathways.
  • Combining antiangiogenic drugs with distinct mechanisms is a strategy to overcome resistance.

Purpose of the Study:

  • To review the preclinical rationale for combining antiangiogenic therapies.
  • To summarize current clinical experience with combination antiangiogenic treatments.
  • To highlight challenges and successes in this therapeutic approach.

Main Methods:

  • Review of preclinical studies on combined antiangiogenic mechanisms.
  • Analysis of early-phase clinical trials evaluating drug combinations.
  • Examination of specific combination examples like sorafenib and bevacizumab.

Main Results:

  • Combination therapies targeting VEGF pathway or angiopoietins show potential.
  • Vascular disrupting agents are also explored in combination strategies.
  • Major responses observed in ovarian carcinoma and glioblastoma with specific combinations.

Conclusions:

  • Combining antiangiogenic agents is a promising strategy to combat resistance.
  • Overlapping and cumulative toxicities present significant challenges.
  • Further research is needed to optimize combination therapies and manage side effects.

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