FLT3 Inhibition in Acute Myeloid Leukaemia - Current Knowledge and Future Prospects.

FLT3 Inhibition in Acute Myeloid Leukaemia - Current Knowledge and Future Prospects. Curr Cancer Drug Targets. 2020 May 17;: Authors: Hogan FL, Williams V, Knapper S Abstract Activating mutations of FMS-like tyrosine kinase 3 (FLT3) are present in 30% of acute myeloid leukaemia (AML) patients at diagnosis and confer an adverse clinical prognosis. Mutated FLT3 has emerged as a viable therapeutic target and a number of FLT3-directed tyrosine kinase inhibitors have progressed through clinical development over the last 10-15 years. The last two years have seen United States Food and Drug Administration (US FDA) approvals of the multi-kinase inhibitor midostaurin for newly-diagnosed FLT3-mutated patients when used in combination with intensive chemotherapy, and of the more FLT3-selective agent gilteritinib, used as monotherapy, for patients with relapsed or treatment-refractory FLT3-mutated AML. The 'second generation' agents quizartinib and crenolanib are also both at advanced stages of clinical development. Significant challenges remain, crucially in negotiating a variety of potential acquired drug resistance mechanisms and in optimising sequencing of FLT3 inhibitory drugs with existing and novel treatment approaches in different clinical settings including frontline therapy, relapsed/refractory disease and maintenance treatment. In this review, we discuss the biology of FLT3, the clinical challenge posed by FLT3-mutated AML, the develo...
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research