ArticleOncotarget2016
Dual inhibition of AKT/FLT3-ITD by A674563 overcomes FLT3 ligand-induced drug resistance in FLT3-ITD positive AML.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Recent Advances in FLT3-Based Dual Inhibitors: A Promising Strategy for the Treatment of Acute Myeloid Leukemia.Current medicinal chemistry · 2026Review
- A Combinatorial Functional Precision Medicine Platform for Rapid Therapeutic Response Prediction in AML.Cancer medicine · 2024Article
- Update on Small Molecule Targeted Therapies for Acute Myeloid Leukemia.Current treatment options in oncology · 2023Review
- Increasing Role of Targeted Immunotherapies in the Treatment of AML.International journal of molecular sciences · 2022Review
- A review of FLT3 inhibitors in acute myeloid leukemia.Blood reviews · 2022Review
- Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.OncoTargets and therapy · 2022Review
- Review
- Discovery of a highly selective VEGFR2 kinase inhibitor CHMFL-VEGFR2-002 as a novel anti-angiogenesis agent.Acta pharmaceutica Sinica. B · 2020Article
- Overcoming adaptive therapy resistance in AML by targeting immune response pathways.Science translational medicine · 2019Article
- Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches.Therapeutic advances in hematology · 2019Review
- Article
- Nuclear membrane-localised NOX4D generates pro-survival ROS in FLT3-ITD-expressing AML.Oncotarget · 2017Article
- Predicting Chemotherapy Resistance in AML.Current hematologic malignancy reports · 2017Review
- Mechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment.Hematology/oncology clinics of North America · 2017Review
Corrections and comments
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Authors and funding
21 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The FLT3-ITD mutation is one of the most prevalent oncogenic mutations in AML. Several FLT3 kinase inhibitors have shown impressive activity in clinical evaluation, however clinical responses are usually transient and clinical effects are rapidly lost due to drug resistance. One of the resistance mechanisms in the AML refractory patients involves FLT3-ligand induced reactivation of AKT and/or ERK signaling via FLT3 wt kinase. Via a screen of numerous AKT kinase inhibitors, we identified the well-established orally available AKT inhibitor, A674563, as a dual suppressor of AKT and FLT3-ITD. A674563 suppressed FLT3-ITD positive AML both in vitro and in vivo. More importantly, compared to other FLT3 inhibitors, A674563 is able to overcome FLT3 ligand-induced drug resistance through simultaneous inhibition of FLT3-ITD- and AKT-mediated signaling. Our findings suggest that A674563 might be a potential drug candidate for overcoming FLT3 ligand-mediated drug resistance in FLT3-ITD positive AML.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.