TY - JOUR
T1 - Therapy of acute myeloid leukemia
T2 - therapeutic targeting of tyrosine kinases
AU - Cioccio, Joseph
AU - Claxton, David
N1 - Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/4/3
Y1 - 2019/4/3
N2 - Introduction: Tyrosine kinases (TKs) drive cell survival and proliferation in many normal and malignant cell types. TKs are frequently mutated in acute myeloid leukemia (AML) and hence are increasingly targeted. The management of AML has dramatically improved because of TKI-targeted treatment. Areas Covered: This review provides a biological background for TK inhibitors (TKIs) in AML and reviews their use in the clinic. TK expression and mutation in AML are explored with a focus on TKs associated with specific AML subsets and treatment outcomes. TKIs that specifically target FLT3, c-Kit, and Jak2 are discussed. TKI targeting of specific genes mutated in individual cases and general ‘untargeted’ use of these agents are highlighted. Lastly, the mechanisms TKI drug resistance in AML are explored. Expert Opinion: The use of TKIs in the clinic is improving outcomes for many patients. An improved understanding of tyrosine kinase biology and the expanding use of TKIs are likely to dramatically improve outcomes in the coming decade. TKIs and other targeted agents could gradually supplant the use of cytotoxic chemotherapy for AML.
AB - Introduction: Tyrosine kinases (TKs) drive cell survival and proliferation in many normal and malignant cell types. TKs are frequently mutated in acute myeloid leukemia (AML) and hence are increasingly targeted. The management of AML has dramatically improved because of TKI-targeted treatment. Areas Covered: This review provides a biological background for TK inhibitors (TKIs) in AML and reviews their use in the clinic. TK expression and mutation in AML are explored with a focus on TKs associated with specific AML subsets and treatment outcomes. TKIs that specifically target FLT3, c-Kit, and Jak2 are discussed. TKI targeting of specific genes mutated in individual cases and general ‘untargeted’ use of these agents are highlighted. Lastly, the mechanisms TKI drug resistance in AML are explored. Expert Opinion: The use of TKIs in the clinic is improving outcomes for many patients. An improved understanding of tyrosine kinase biology and the expanding use of TKIs are likely to dramatically improve outcomes in the coming decade. TKIs and other targeted agents could gradually supplant the use of cytotoxic chemotherapy for AML.
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U2 - 10.1080/13543784.2019.1584610
DO - 10.1080/13543784.2019.1584610
M3 - Review article
C2 - 30775933
AN - SCOPUS:85062360330
SN - 1354-3784
VL - 28
SP - 337
EP - 349
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 4
ER -