ArticleHaematologica2022
AXL/MERTK inhibitor ONO-7475 potently synergizes with venetoclax and overcomes venetoclax resistance to kill
Article in Haematologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Anexelekto (Axl)/Mer Inhibitor Tamnorzatinib in Patients with Relapsed/Refractory Acute Myeloid Leukaemia: Results from a Phase I (Monotherapy) and Phase II (Combination with Venetoclax) Clinical Study.Acta haematologica · 2026Trial
- Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.Cancer research communications · 2026Article
- RGX-019-MMAE inhibits leukemia progression by targeting MER proto-oncogene tyrosine kinase (MERTK) in acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2026Article
- MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis.Nature communications · 2025Article
- Integrated stress response activation induced by usnic acid alleviates BCL-2 inhibitor ABT-199 resistance in acute myeloid leukemia.Journal of advanced research · 2025Article
- Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment.Small science · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- MERTK Inhibition as a Targeted Novel Cancer Therapy.International journal of molecular sciences · 2024Review
- FLT3-Mutated Leukemic Stem Cells: Mechanisms of Resistance and New Therapeutic Targets.Cancers · 2024Review
- MerTK Drives Proliferation and Metastatic Potential in Triple-Negative Breast Cancer.International journal of molecular sciences · 2024Article
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- Effects of Combined Therapeutic Targeting of AXL and ATR on Pleural Mesothelioma Cells.Molecular cancer therapeutics · 2024Article
- Investigating resistance to 5-Azacytidine and Venetoclax in PDX models of MDS/AML.Frontiers in oncology · 2024Article
- Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers.Cancers · 2023Review
- Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions.Cancers · 2023Review
- Drugging the efferocytosis process: concepts and opportunities.Nature reviews. Drug discovery · 2022Review
- Review
- The Growing Role of the BH3 Mimetic Drug Venetoclax in the Therapy of Acute Myeloid Leukemia.Mediterranean journal of hematology and infectious diseases · 2022Review
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
FMS-like Tyrosine Kinase 3 (FLT3) mutation is associated with poor survival in acute myeloid leukemia (AML). The specific Anexelekto/MER Tyrosine Kinase (AXL) inhibitor, ONO-7475, kills FLT3-mutant AML cells with targets including Extracellular- signal Regulated Kinase (ERK) and Myeloid Cell Leukemia 1 (MCL1). ERK and MCL1 are known resistance factors for Venetoclax (ABT-199), a popular drug for AML therapy, prompting the investigation of the efficacy of ONO-7475 in combination with ABT-199 in vitro and in vivo. ONO-7475 synergizes with ABT-199 to potently kill FLT3-mutant acute myeloid leukemia cell lines and primary cells. ONO-7475 is effective against ABT-199-resistant cells including cells that overexpress MCL1. Proteomic analyses revealed that ABT-199-resistant cells expressed elevated levels of pro-growth and anti-apoptotic proteins compared to parental cells, and that ONO-7475 reduced the expression of these proteins in both the parental and ABT-199-resistant cells. ONO-7475 treatment significantly extended survival as a single in vivo agent using acute myeloid leukemia cell lines and PDX models. Compared to ONO-7474 monotherapy, the combination of ONO-7475/ABT-199 was even more potent in reducing leukemic burden and prolonging the survival of mice in both model systems. These results suggest that the ONO-7475/ABT-199 combination may be effective for AML therapy.
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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.