Impact of tivozanib on patient outcomes in treatment of advanced renal cell carcinoma.

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Yalcin S, Lacin S

Impact of tivozanib on patient outcomes in treatment of advanced renal cell carcinoma.

Cancer Manag Res. 2019 Aug 16;11:7779-7785. doi: 10.2147/CMAR.S206105. eCollection 2019.

PubMed ID

31496820 [ View in PubMed

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Abstract

Renal cell carcinoma (RCC) is the most common type of kidney malignancy, and the clear-cell subtype represents the majority of RCCs. RCC is a heterogeneous disease in terms of genetic and histological features which determine the behavior of the disease. The von Hippel-Lindau (VHL) is a tumor suppressor gene and mutations of this gene are seen in 95% of clear-cell RCCs. Inactivation of VHL causes the accumulation of hypoxia-inducible factor-1 (HIF-1), and in turn, accumulation of HIF-1 induces overexpression of vascular endothelial growth factor (VEGF); the increase in VEGF expression makes RCC a highly vascularized tumor, and forms the rationale for antiVEGF treatment. In the past decade, improvement in the survival of RCC patients has been observed due to new effective therapies, such as antiVEGF and mammalian target of rapamycin (mTOR) targeting agents and immune checkpoint inhibitors. The majority of VEGF targeted agents are not just selective to VEGF receptors, but usually also have inhibitory effects on other kinases, such as c-KIT and FLT3. Tivozanib is an extremely potent and selective tyrosine kinase inhibitor (TKI) of VEGFR-1, 2, and 3, with a relatively long half-life, that is approved by the European Commission for the treatment of advanced/metastatic RCC. Tivozanib, at very low serum concentration can inhibit phosphorylation of VEGFR -1, -2, and -3 tyrosine kinase activity. This article summarizes the clinical data on tivozanib in the treatment of advanced/metastatic RCC.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tivozanib	Mast/stem cell growth factor receptor Kit	Protein	Humans	Yes	Inhibitor	Details
Tivozanib	Receptor-type tyrosine-protein kinase FLT3	Protein	Humans	Unknown	Inhibitor	Details