Background: Angiogenesis is a mechanism, which tumors use to recruit oxygen and nutrients in order to maintain growth. The vascular endothelial growth factor family is the primary mediator of this process. For the last couple of decades, inhibition of angiogenesis has been the subject of extensive research, but so far anti-angiogenic drugs have only shown a modest effect.
Methods: This paper reviews four relevant anti-angiogenic drugs: bevacizumab, ramucirumab, nintedanib and sunitinib. The primary focus will be recent trials investigating the effects of the drugs in lung, breast and gastrointestinal cancers. Furthermore, there will be a discussion of unsolved problems, such as lack of biomarkers, drug resistance, and adverse events, for which a solution is necessary in order to improve the benefit of anti-angiogenic drugs in the future.
Results: Anti-angiogenic therapy is extensively used in the treatment of cancer. There is evidence that drug-induced hypertension serves as a biomarker for a good response to therapy. Currently several possible anti-angiogenic biomarkers are under discussion. Further examples are changes in VEGF or interleukin (IL)-8 polymorphisms, changed plasma levels of VEGF, or tumor microvessel density. To overcome therapyassociated problems, more research for valid biomarkers is necessary. In addition, a strategy to overcome resistance problems and severe adverse events is desirable.
Conclusion: Clinical trials evaluating targeted therapies with specificity for resistance mechanisms are necessary. Moreover, biomarker studies in future clinical investigations are important for the development of the next generation of anti-angiogenic drugs.
Keywords: Cancer, angiogenesis, tyrosine kinase inhibitors, bevacizumab, ramucirumab, nintedanib, sunitinib.
Editorial [Hot Topic: Molecular Targeted Therapy of Gastrointestinal Cancer (Guest Editor: Marcus W. Wiedmann)]
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