Modes of resistance to anti-angiogenic therapy.
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.
Bergers
Gabriele
G
University of California, San Francisco, Department of Neurological Surgery, Brain Tumour Research Center, San Francisco, California 94143, USA. gabriele.bergers@ucsf.edu
Hanahan
Douglas
D
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D042442:Vascular Endothelial Growth Factors / Q000187:drug effects* / Q000502:physiology
D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors