Can FLT3 inhibitors overcome resistance in AML?
The identification of FLT3 mutations across a range of the cytogenetic subgroups of AML has opened up the possibility of a targeted therapeutic approach with broad applicability. Four agents are currently in clinical trials, at least 3 of which have both sufficient activity against AML and sufficiently acceptable toxicity profiles to support continued efforts to refine their inclusion into therapeutic regimens for AML. Better understanding of the genetics of inherent and acquired resistance is needed to guide development of second-generation agents. Optimizing the integration of FLT3 inhibitor therapy with chemotherapy has the potential both to decrease toxicity and improve response.
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Winnie F
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Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Gary Gilliland
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005663:Furans; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D019311:Staurosporine / Q000627:therapeutic use; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics
D000970:Antineoplastic Agents; D002227:Carbazoles; D005663:Furans; D007211:Indoles; D010879:Piperazines; D011799:Quinazolines; C119379:lestaurtinib; C464670:tandutinib; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; D019311:Staurosporine