title: 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 some hematological malignancies. Future studies should focus on the exploration of biomarkers to screen sensitive patients and concomitant or metronomic dosage with other kinds of medicines.
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin, China.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Zhao
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory of Longevity and Aging-Related Diseases, Ministry of Education Beijing, China; Center for Translational Medicine, Guangxi Medical University Nanning, Guangxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital Tianjin, China.
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Zhou
keywords: Angiogenesis inhibitors; neoplasms; pazopanib