TY - JOUR
T1 - Molecularly Targeted Therapy in Acute Myeloid Leukemia
T2 - Current Treatment Landscape and Mechanisms of Response and Resistance
AU - Lachowiez, Curtis A.
AU - DiNardo, Courtney D.
AU - Loghavi, Sanam
N1 - Publisher Copyright:
© 2023 by the authors.
PY - 2023/3
Y1 - 2023/3
N2 - Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, we comprehensively review the current landscape of IDH and FLT3 inhibitors in clinical practice for the treatment of AML, highlight known resistance mechanisms, and discuss new cellular or molecularly targeted therapies currently under investigation in ongoing early phase clinical trials.
AB - Treatment for acute myeloid leukemia (AML) has evolved rapidly over the last decade as improved understanding of cytogenetic and molecular drivers of leukemogenesis refined survival prognostication and enabled development of targeted therapeutics. Molecularly targeted therapies are now approved for the treatment of FLT3 and IDH1/2-mutated AML and additional molecularly and cellularly targeted therapeutics are in development for defined patient subgroups. Alongside these welcome therapeutic advancements, increased understanding of leukemic biology and treatment resistance has resulted in clinical trials investigating combinations of cytotoxic, cellular, and molecularly targeted therapeutics resulting in improved response and survival outcomes in patients with AML. Herein, we comprehensively review the current landscape of IDH and FLT3 inhibitors in clinical practice for the treatment of AML, highlight known resistance mechanisms, and discuss new cellular or molecularly targeted therapies currently under investigation in ongoing early phase clinical trials.
KW - FLT3 inhibitor
KW - IDH inhibitor
KW - acute myeloid leukemia
KW - targeted therapy
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U2 - 10.3390/cancers15051617
DO - 10.3390/cancers15051617
M3 - Review article
C2 - 36900407
AN - SCOPUS:85149891886
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 5
M1 - 1617
ER -