TY - JOUR
T1 - FLT3 tyrosine kinase inhibitors in acute myeloid leukemia
T2 - Clinical implications and limitations
AU - Kayser, Sabine
AU - Levis, Mark J.
N1 - Funding Information:
This work was supported by grants from the Else Krö ner-Fresenius-Stiftung (Forschungskolleg Ulm, 2010_Kolleg.24; to S.K.), the National Cancer Institute (Specialized Programs of Research Excellence [SPORE] leukemia grants P50 CA100632-06 and R01 CA128864) and the American Society of Clinical Oncology (to M.J.L.). M.J.L. is a Clinical Scholar of the Leukemia & Lymphoma Society.
PY - 2014/2
Y1 - 2014/2
N2 - Internal tandem duplications of the FMS-like tyrosine kinase 3 (FLT3) gene are one of the most frequent gene mutations in acute myeloid leukemia (AML) and are associated with poor clinical outcome. The remission rate is high with intensive chemotherapy, but most patients eventually relapse. During the last decade, FLT3 mutations have emerged as an attractive target for a molecularly specific treatment strategy. Targeting FLT3 receptor tyrosine kinases in AML has shown encouraging results in the treatment of FLT3 mutated AML, but in most patients responses are incomplete and not sustained. Newer, more specific compounds seem to have a higher potency and selectivity against FLT3. During therapy with FLT3 tyrosine kinase inhibitors (TKIs) the induction of acquired resistance has emerged as a clinical problem. Therefore, optimization of the targeted therapy and potential treatment options to overcome resistance is currently the focus of clinical research. In this review we discuss the use and limitations of TKIs as a therapeutic strategy for the treatment of FLT3 mutated AML, including mechanisms of resistance to TKIs as well as possible novel strategies to improve FLT3 inhibitor therapy.
AB - Internal tandem duplications of the FMS-like tyrosine kinase 3 (FLT3) gene are one of the most frequent gene mutations in acute myeloid leukemia (AML) and are associated with poor clinical outcome. The remission rate is high with intensive chemotherapy, but most patients eventually relapse. During the last decade, FLT3 mutations have emerged as an attractive target for a molecularly specific treatment strategy. Targeting FLT3 receptor tyrosine kinases in AML has shown encouraging results in the treatment of FLT3 mutated AML, but in most patients responses are incomplete and not sustained. Newer, more specific compounds seem to have a higher potency and selectivity against FLT3. During therapy with FLT3 tyrosine kinase inhibitors (TKIs) the induction of acquired resistance has emerged as a clinical problem. Therefore, optimization of the targeted therapy and potential treatment options to overcome resistance is currently the focus of clinical research. In this review we discuss the use and limitations of TKIs as a therapeutic strategy for the treatment of FLT3 mutated AML, including mechanisms of resistance to TKIs as well as possible novel strategies to improve FLT3 inhibitor therapy.
KW - Acute myeloid leukemia
KW - FLT3 mutations
KW - Mechanism of resistance
KW - Molecular tailored therapy
KW - Tyrosine kinase inhibitors
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U2 - 10.3109/10428194.2013.800198
DO - 10.3109/10428194.2013.800198
M3 - Review article
C2 - 23631653
AN - SCOPUS:84894255030
SN - 1042-8194
VL - 55
SP - 243
EP - 255
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 2
ER -