Quizartinib for the treatment of FLT3/ITD acute myeloid leukemia
- PMID: 25145428
- PMCID: PMC6081740
- DOI: 10.2217/fon.14.105
Quizartinib for the treatment of FLT3/ITD acute myeloid leukemia
Abstract
FLT3/ITD acute myeloid leukemia is a poor prognosis disease driven by a constitutively activated receptor tyrosine kinase, making it an obvious target for drug development. The development of clinically effective FLT3 inhibitors has been slow, in part because many are multi-targeted inhibitors that are not selective or specific for FLT3. Quizartinib is the first small molecule FLT3 tyrosine kinase inhibitor expressly developed as a FLT3 inhibitor. It is potent, selective and has ideal pharmacokinetics in comparison to other compounds previously tested. This article summarizes its advantages and limitations, and details the insights into the biology of the disease that have been uncovered through the laboratory and clinical use of quizartinib.
Keywords: FLT3; c-KIT; kinase; leukemia; quizartinib.
Conflict of interest statement
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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References
-
- Burnett A, Wetzler M, Lowenberg B. Therapeutic advances in acute myeloid leukemia. J Clin Oncol. 2011;29(5):487–494. - PubMed
-
- Lo-Coco F, Awisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111–121. - PubMed
-
- Wouters BJ, Lowenberg B, Erpelinck-Verschueren CA, et al. Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113(13):3088–3091. - PMC - PubMed
-
- Levis M, Small D. FLT3: it does matter in leukemia. Leukemia. 2003;17(9):1738–1752. Review of the clinical and biologic features of FLT3/ITD acute myeloid leukemia. - PubMed
-
- Kiyoi H, Ohno R, Ueda R, Saito H, Naoe T. Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene. 2002;21(16):2555–2563. - PubMed
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