TY - JOUR
T1 - FLT3 inhibitors for acute myeloid leukemia
T2 - A review of their efficacy and mechanisms of resistance
AU - Grunwald, Michael R.
AU - Levis, Mark J.
PY - 2013/6
Y1 - 2013/6
N2 - Since the Food and Drug Administration approval of imatinib for treatment of chronic myeloid leukemia in 2001, tyrosine kinase inhibitors (TKIs) have become a mainstay in the care of many malignancies. In acute myeloid leukemia (AML), activating mutations in the FMS-like tyrosine kinase 3 (FLT3) gene result in survival and proliferation of leukemic blasts and are associated with adverse prognosis. Therefore, the FLT3 receptor is an appealing target for inhibition. Multiple small molecule TKIs are currently in development for FLT3-mutated AML, and agents are beginning to show promising efficacy. In other malignancies, the development of resistance to TKIs during the course of therapy has proven to be a challenge, and thus far, in clinical trials of FLT3 TKIs, resistance to inhibition represents a significant barrier to successful FLT3 inhibition. Understanding the mechanisms of resistance and overcoming these obstacles to target inhibition will be central to the success of these agents.
AB - Since the Food and Drug Administration approval of imatinib for treatment of chronic myeloid leukemia in 2001, tyrosine kinase inhibitors (TKIs) have become a mainstay in the care of many malignancies. In acute myeloid leukemia (AML), activating mutations in the FMS-like tyrosine kinase 3 (FLT3) gene result in survival and proliferation of leukemic blasts and are associated with adverse prognosis. Therefore, the FLT3 receptor is an appealing target for inhibition. Multiple small molecule TKIs are currently in development for FLT3-mutated AML, and agents are beginning to show promising efficacy. In other malignancies, the development of resistance to TKIs during the course of therapy has proven to be a challenge, and thus far, in clinical trials of FLT3 TKIs, resistance to inhibition represents a significant barrier to successful FLT3 inhibition. Understanding the mechanisms of resistance and overcoming these obstacles to target inhibition will be central to the success of these agents.
KW - Acute myeloid leukemia (AML)
KW - FLT3
KW - Tyrosine kinase inhibitor (TKI)
UR - http://www.scopus.com/inward/record.url?scp=84879132548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879132548&partnerID=8YFLogxK
U2 - 10.1007/s12185-013-1334-8
DO - 10.1007/s12185-013-1334-8
M3 - Review article
C2 - 23613268
AN - SCOPUS:84879132548
SN - 0925-5710
VL - 97
SP - 683
EP - 694
JO - International journal of hematology
JF - International journal of hematology
IS - 6
ER -