Modes of Resistance to Anti-Angiogenic Therapy

Nat Rev Cancer. 2008 Aug;8(8):592-603. doi: 10.1038/nrc2442.

Abstract

Angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signalling pathways are affording demonstrable therapeutic efficacy in mouse models of cancer and in an increasing number of human cancers. However, in both preclinical and clinical settings, the benefits are at best transitory and are followed by a restoration of tumour growth and progression. Emerging data support a proposition that two modes of unconventional resistance underlie such results: evasive resistance, an adaptation to circumvent the specific angiogenic blockade; and intrinsic or pre-existing indifference. Multiple mechanisms can be invoked in different tumour contexts to manifest both evasive and intrinsic resistance, motivating assessment of their prevalence and importance and in turn the design of pharmacological strategies that confer enduring anti-angiogenic therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Drug Resistance, Neoplasm*
  • Humans
  • Neoplasms / blood supply*
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / pathology
  • Signal Transduction / drug effects
  • Vascular Endothelial Growth Factors / drug effects*
  • Vascular Endothelial Growth Factors / physiology

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factors