Biomarkers of angiogenesis and their role in the development of VEGF inhibitors.
Vascular endothelial growth factor (VEGF) has been confirmed as an important therapeutic target in randomised clinical trials in multiple disease settings. However, the extent to which individual patients benefit from VEGF inhibitors is unclear. If we are to optimise the use of these drugs or develop combination regimens that build on this efficacy, it is critical to identify those patients who are likely to benefit, particularly as these agents can be toxic and are expensive. To this end, biomarkers have been evaluated in tissue, in circulation and by imaging. Consistent drug-induced increases in plasma VEGF-A and blood pressure, as well as reductions in soluble VEGF-R2 and dynamic contrast-enhanced MRI parameters have been reported. In some clinical trials, biomarker changes were statistically significant and associated with clinical end points, but there is considerable heterogeneity between studies that are to some extent attributable to methodological issues. On the basis of observations with these biomarkers, it is now appropriate to conduct detailed prospective studies to define a suite of predictive, pharmacodynamic and surrogate response biomarkers that identify those patients most likely to benefit from and monitor their response to this novel class of drugs.
Murukesh
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Department of Medical Oncology, Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Cancer Research UK and University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, UK.
Dive
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Jayson
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D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000068258:Bevacizumab; D015415:Biomarkers; D001794:Blood Pressure / Q000187:drug effects; D015687:Cell Hypoxia; D003287:Contrast Media; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D009369:Neoplasms / Q000097:blood / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D018579:Patient Selection; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D016032:Randomized Controlled Trials as Topic; D040262:Receptors, Vascular Endothelial Growth Factor / Q000097:blood* / Q000187:drug effects; D012107:Research Design; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics / Q000276:immunology
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D015415:Biomarkers; D003287:Contrast Media; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor