Abstract
Advanced urothelial cancer (UC) is a lethal disease despite current advances in systemic therapy, including platinum chemotherapy combinations and immune checkpoint inhibition. Tumor angiogenesis is involved in UC growth and metastatic progression. Proangiogenic signaling through the VEGFR is a key process in UC with prognostic significance. Targeting of VEGFR2 with the monoclonal antibody ramucirumab has been tested in various different tumor types. In this review, we discuss the development of the drug in the context of its preclinical and clinical use with a focus on UC. Improvements in our ability to predict responses and resistance are key for maximizing its efficacy and selecting the most appropriate combinations with other active agents.
Keywords:
VEGFR; angiogenesis; bladder cancer; monoclonal antibody; ramucirumab; targeted therapy; urothelial carcinoma.
MeSH terms
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / adverse effects
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized
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Disease-Free Survival
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Humans
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Neoplasm Metastasis
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Neoplasms / drug therapy*
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Neoplasms / genetics
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Neoplasms / pathology
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Neovascularization, Pathologic / drug therapy*
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Neovascularization, Pathologic / pathology
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Ramucirumab
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Urothelium / drug effects*
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Urothelium / pathology
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-2 / genetics
Substances
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Angiogenesis Inhibitors
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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KDR protein, human
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factor Receptor-2