期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 13, 期 -, 页码 1117-1125出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S198950
关键词
quizartinib; FLT3 inhibitor; FLT3-ITD mutation; AML; clinical trials; targeted therapy
资金
- National Natural Science Foundation of China [81170492, 81370673]
- National High Technology Research and Development Program 863 of People's Republic of China [2012AA022703]
- National Key Basic Research Program 973 of People's Republic of China [2010CB732404]
- Key Medical Projects of Jiangsu Province [BL2014078]
- Key Medical of Jiangsu Province [ZDXKB2016020]
- Jiangsu Social Development Project [BE2018711]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [SJCX18-0068]
Quizartinib is an effective therapy for patients with FLT3-ITD acute myeloid leukemia (AML) by continuing to inhibit the activity of FLT3 gene, leading to apoptosis of tumor cells. Multiple clinical trials have proved that it is effective in relapsed or refractory AML with an FLT3-ITD mutation. In this review, we focus on the characteristics of FLT3/ITD mutations, the mechanism and pharmacokinetics of quizartinib, and the mechanisms of resistance to quizartinib. We also summarize clinical experiences and adverse effects with quizartinib and recommend crucial approaches of quizartinib in the therapy of patients with newly diagnosed AML and patients with relapsed/refractory AML, particularly those with FLT3-ITD mutation. Quizartinib presents its advantages as a very promising agent in the treatment of AML, especially in patients with FLT3-ITD mutations. FLT3/ITD mutation can lead to constitutive autophosphorylation of FLT3 and activation of its downstream effectors including RAS/RAF/MEK, MAPK/ERK, PI3K/AKT/mTOR and JAK/STAT5 signal pathways, while Quizartinib can inhibit these downstream pathways through specific FLT3 inhibition. Quizartinib has received US Food and Drug Administration breakthrough therapy designation in patients with relapsed/refractory FLT3-ITD AML based on clinical trials. A larger sample of clinical trials are needed to verify its safety and efficacy, and the efficacy of quizartinib combined with chemotherapy or allogeneic hematopoietic cell transplantation should also be estimated in clinical trials. Meanwhile, for the side effects of quizartinib, further studies are needed to find a way to reduce its toxicity.
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