Overview of fundamental study of pazopanib in cancer
Abstract
Angiogenesis is an indispensible process for tumor growth and metastasis. Anti-angiogenesis based therapy is one of the most promising treatments for inhibiting cancer progression. Through the exploration of inhibitors of vascular endothelial growth factor receptor (VEGFR)-2, deemed as the major angiogenesis pathway, pazopanib was found as a small molecular pan-VEGFR and pan-platelet-derived growth factor receptor (PDGFR) inhibitor, with suitable pharmacodynamic and pharmacokinetic parameters to be an oral drug. In an vitro study, pazopanib exerted anti-tumor effect through mechanisms including the Raf-MAPK/ERK (MEK)-extracellular signal-regulated kinase (ERK) pathway, and directly targeted on v-raf murine sarcoma viral oncogene homolog B (B-raf) as well. It inhibited the proliferation of cell lines, such as DU-145 and HRC-45 in hepatocellular carcinoma, through mechanisms like "cell cycle arrest." In vivo xenograft studies and phase I/II clinical trials revealed a series of plasma cytokine and angiogenic factors, such as interleukin (IL)-6, IL-12, hepatocyte growth factor (HGF), and soluble VEGFR2, which have significant association with clinical curative effect. Pazopanib has been shown to be effective in solid tumors and som...Continue Reading
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