ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 72 citations in OpenAlex.
- Aberrant expression of MERTK activates BCR via CD79a in CLL cells: alternative therapeutic strategy for relapsed/refractory CLL.Leukemia · 2026Article
- Dual Therapeutic Impact of AXL Inhibitor AB-329: Chemotherapy Sensitization and Immune Microenvironment Reprogramming in TNBC.International journal of molecular sciences · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Aberrantly Expressed Mitochondrial Lipid Kinase, AGK, Activates JAK2-Histone H3 Axis and BCR Signal: A Mechanistic Study with Implication in CLL Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The role of the nervous system in the occurrence, development, and immune response of renal cell carcinoma.Frontiers in immunology · 2025Review
- RNAi Screen Identifies AXL Inhibition Combined with Cannabinoid WIN55212-2 as a Potential Strategy for Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2024Article
- AXL as immune regulator and therapeutic target in Acute Myeloid Leukemia: from current progress to novel strategies.Experimental hematology & oncology · 2024Review
- Aberrant activation of AXL may drive progression of squamous cell carcinoma in CLL patients: a mechanistic study with clinical implications.British journal of cancer · 2024Article
- Article
- AXL Inhibition Improves the Antitumor Activity of Chimeric Antigen Receptor T Cells.Cancer immunology research · 2023Article
- AXL Inhibitors: Status of Clinical Development.Current oncology reports · 2023Review
- Repurposing Axl Kinase Inhibitors for the Treatment of Respiratory Syncytial Virus Infection.Antimicrobial agents and chemotherapy · 2023Article
- Structure-based discovery of potent inhibitors of Axl: design, synthesis, and biological evaluation.RSC medicinal chemistry · 2022Article
- The Development of AXL Inhibitors in Lung Cancer: Recent Progress and Challenges.Frontiers in oncology · 2022Review
- Dissecting the Role of AXL in Cancer Immune Escape and Resistance to Immune Checkpoint Inhibition.Frontiers in immunology · 2022Review
- The Relationship ofJournal of clinical medicine · 2021Article
- Gas6/Axl signaling pathway promotes proliferation, migration and invasion and inhibits apoptosis in A549 cells.Experimental and therapeutic medicine · 2021Article
- Therapeutic Targeting of the Gas6/Axl Signaling Pathway in Cancer.International journal of molecular sciences · 2021Review
- SIRT3 overexpression and epigenetic silencing of catalase regulate ROS accumulation in CLL cells activating AXL signaling axis.Blood cancer journal · 2021Article
- Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
purposeB-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL B-cell survival. Here, we explored the possibility of using a high-affinity Axl inhibitor as a single agent or in combination with Bruton's tyrosine kinase (BTK) inhibitors for future clinical trial to treat patients with CLL. EXPERIMENTAL
designExpression/activation status of other members of the TAM (e.g., Tyro3, Axl, and MER) family of RTKs in CLL B cells was evaluated. Cells were treated with a high-affinity orally bioavailable Axl inhibitor TP-0903 with or without the presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on the Axl signaling pathway were also evaluated in CLL B cells. Finally, cells were exposed to TP-0903 in combination with BTK inhibitors to determine any synergistic/additive effects of the combination.
resultsCLL B cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and forms a complex with Axl in CLL B cells. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges. Importantly, CLL BMSCs could not protect the leukemic B cells from TP-0903-induced apoptosis. A marked reduction of the antiapoptotic proteins Mcl-1, Bcl-2, and XIAP and upregulation of the proapoptotic protein BIM in CLL B cells was detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis.
conclusionsAdministration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL.
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What OpenQuestion holds
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.