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已发表论文
Crenolanib（血小板衍生生长因子受体抑制剂），一个 PDGFR 抑制剂，抑制体内肺癌细胞增殖并抑制肿瘤生长
Authors Wang P, Song L, Ge H, Jin P, Jiang Y, Hu W, Geng N
Published Date September 2014 Volume 2014:7 Pages 1761—1768
DOI http://dx.doi.org/10.2147/OTT.S68773
Received 3 June 2014, Accepted 4 July 2014, Published 26 September 2014
Abstract: Platelet-derived growth factor (PDGF) and its receptors (PDGFR), including PDGFRα and PDGFRβ, play important roles in tumorigenesis, tumor progression, and the regulation of stromal cell function. Constitutive activation of PDGFR signaling, gene rearrangement, and activating mutations of PDGFR have been identified in various types of human tumors and malignancies. PDGFRα and PDGFRβ belong to the family of type III receptor tyrosine kinases and, upon stimulation, activate downstream signaling cascades. Crenolanib is a specific tyrosine kinase inhibitor that targets and inhibits the kinase activity of PDGFR and the FMS-related tyrosine kinase 3. Its clinical efficacy in several human tumors is currently under investigation in Phase II clinical trials. In this study, we examined the potential role of crenolanib in the treatment of non-small-cell lung cancer (NSCLC). Using A549 cells as a model system, we have shown that crenolanib is capable of suppressing proliferation and inducing apoptosis in a dose-dependent manner. Crenolanib-treated cells have reduced migratory activity in response to inducers of chemotaxis. Furthermore, the in vivo antitumor activity of crenolanib was confirmed in an NSCLC xenograft tumor model. Injection of crenolanib significantly inhibited the growth of tumor mass by inducing apoptosis in tumor cells. Our results provide strong evidence supporting the use of crenolanib as a potential therapeutic agent in treating NSCLC. This work sets a foundation for further development of targeted and personalized therapeutics for lung cancer.
Keywords: platelet-derived growth factor receptor signaling, receptor tyrosine kinase, tyrosine kinase inhibitor, non-small-cell lung cancer, chemotherapy, targeted therapy
Keywords: platelet-derived growth factor receptor signaling, receptor tyrosine kinase, tyrosine kinase inhibitor, non-small-cell lung cancer, chemotherapy, targeted therapy
