TY - JOUR
T1 - Investigational FMS-like tyrosine kinase 3 inhibitors in treatment of acute myeloid leukemia
AU - Pemmaraju, Naveen
AU - Kantarjian, Hagop
AU - Andreeff, Michael
AU - Cortes, Jorge
AU - Ravandi, Farhad
N1 - Funding Information:
J Cortes is a consultant for Novartis, Astellas, and has received research support from Ambit, Arog, Astellas, Novartis, Ariad and CTI Pharmaceuticals. M Andreeff is supported by Bayer and Onyx Pharmaceuticals. 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.
PY - 2014/7
Y1 - 2014/7
N2 - Introduction: Outcomes for the majority of patients with acute myeloid leukemia (AML) remain poor. Over the past decade, significant progress has been made in the understanding of the cytogenetic and molecular determinants of AML pathogenesis. One such advance is the identification of recurring mutations in the FMS-like tyrosine kinase 3 gene (FLT3). Currently, this marker, which appears in approximately one-third of all AML patients, not only signifies a poorer prognosis but also identifies an important target for therapy. FLT3 inhibitors have now undergone clinical evaluation in Phase I, II and III clinical trials, as both single agents and in combination with chemotherapeutics. Unfortunately, to date, none of the FLT3 inhibitors have gained FDA approval for the treatment of patients with AML. Yet, several promising FLT3 inhibitors are being evaluated in all phases of drug development.Areas covered: This review aims to highlight the agents furthest along in their development. It also focuses on those FLT3 inhibitors that are being evaluated in combination with other anti-leukemia agents.Expert opinion: The authors believe that the field of research for FLT3 inhibitors remains promising, despite the historically poor prognosis of this subgroup of patients with AML. The most promising areas of research will likely be the elucidation of the mechanisms of resistance to FLT3 inhibitors, and development of potent FLT3 inhibitors alone or in combination with hypomethylating agents, cytotoxic chemotherapy or with other targeted agents.
AB - Introduction: Outcomes for the majority of patients with acute myeloid leukemia (AML) remain poor. Over the past decade, significant progress has been made in the understanding of the cytogenetic and molecular determinants of AML pathogenesis. One such advance is the identification of recurring mutations in the FMS-like tyrosine kinase 3 gene (FLT3). Currently, this marker, which appears in approximately one-third of all AML patients, not only signifies a poorer prognosis but also identifies an important target for therapy. FLT3 inhibitors have now undergone clinical evaluation in Phase I, II and III clinical trials, as both single agents and in combination with chemotherapeutics. Unfortunately, to date, none of the FLT3 inhibitors have gained FDA approval for the treatment of patients with AML. Yet, several promising FLT3 inhibitors are being evaluated in all phases of drug development.Areas covered: This review aims to highlight the agents furthest along in their development. It also focuses on those FLT3 inhibitors that are being evaluated in combination with other anti-leukemia agents.Expert opinion: The authors believe that the field of research for FLT3 inhibitors remains promising, despite the historically poor prognosis of this subgroup of patients with AML. The most promising areas of research will likely be the elucidation of the mechanisms of resistance to FLT3 inhibitors, and development of potent FLT3 inhibitors alone or in combination with hypomethylating agents, cytotoxic chemotherapy or with other targeted agents.
KW - Crenolanib
KW - FMS-like tyrosine kinase 3 gene
KW - FMS-like tyrosine kinase 3 gene inhibitor
KW - Quizartinib
KW - Sorafenib
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U2 - 10.1517/13543784.2014.911839
DO - 10.1517/13543784.2014.911839
M3 - Review article
C2 - 24749672
AN - SCOPUS:84902340530
SN - 1354-3784
VL - 23
SP - 943
EP - 954
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
IS - 7
ER -