ArticleCommunications biology2023
The effect of inhibition of receptor tyrosine kinase AXL on DNA damage response in ovarian cancer.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 15 citations in OpenAlex.
- Stimuli-responsive structural transformation of adaptive peptide nanomaterials toward biomedical applications.Materials today. Bio · 2026Review
- Hijacking of host PCNA by circovirus replication-associated protein to recruit POLD1 drives viral DNA replication and is inhibited by R428.PLoS pathogens · 2026Article
- Article
- Transcriptomic analysis of zonula occludens-1 (ZO-1) knockout in ovarian cancer cell lines.Genes & genomics · 2026Article
- A fast-progressing orthotopic ovarian cancer model reveals synergistic antitumor effects of AXL-targeting nanobodies and Olaparib.Gynecologic oncology reports · 2025Article
- The Receptor Tyrosine Kinase Axl in (Advanced) Gastric Cancer-From Pathophysiology to Therapeutic Impact.Medicina (Kaunas, Lithuania) · 2025Review
- Signaling networks and MiRNA crosstalk in ovarian cancer chemoresistance.Journal of ovarian research · 2025Review
- Navigating TAM receptor dynamics in tumour immunotherapy.Cancer immunology, immunotherapy : CII · 2025Review
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Understanding DNA replication and replication stress as avenues to combat cancer.Communications biology · 2024Article
- RNAi Screen Identifies AXL Inhibition Combined with Cannabinoid WIN55212-2 as a Potential Strategy for Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Hallmarks of pancreatic cancer: spotlight on TAM receptors.EBioMedicine · 2024Review
- Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer.Acta pharmacologica Sinica · 2024Article
- The golden key to open mystery boxes of SMARCA4-deficient undifferentiated thoracic tumor: focusing immunotherapy, tumor microenvironment and epigenetic regulation.Cancer gene therapy · 2024Review
- Drug resistance in ovarian cancer: from mechanism to clinical trial.Molecular cancer · 2024Review
- Biomarkers in Ovarian Cancer: Towards Personalized Medicine.Proteomes · 2024Review
- The Role of Axl Inhibition and Immune Checkpoint Blockade in Non-small Cell Lung Cancer: Current Understanding and Treatment Strategies.Cancer diagnosis & prognosisReview
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
AXL is a receptor tyrosine kinase that is often overexpressed in cancers. It contributes to pathophysiology in cancer progression and therapeutic resistance, making it an emerging therapeutic target. The first-in-class AXL inhibitor bemcentinib (R428/BGB324) has been granted fast track designation by the U.S. Food and Drug Administration (FDA) in STK11-mutated advanced metastatic non-small cell lung cancer and was also reported to show selective sensitivity towards ovarian cancers (OC) with a Mesenchymal molecular subtype. In this study, we further explored AXL's role in mediating DNA damage responses by using OC as a disease model. AXL inhibition using R428 resulted in the increase of DNA damage with the concurrent upregulation of DNA damage response signalling molecules. Furthermore, AXL inhibition rendered cells more sensitive to the inhibition of ATR, a crucial mediator for replication stress. Combinatory use of AXL and ATR inhibitors showed additive effects in OC. Through SILAC co-immunoprecipitation mass spectrometry, we identified a novel binding partner of AXL, SAM68, whose loss in OC cells harboured phenotypes in DNA damage responses similar to AXL inhibition. In addition, AXL- and SAM68-deficiency or R428 treatment induced elevated levels of cholesterol and upregulated genes in the cholesterol biosynthesis pathway. There might be a protective role of cholesterol in shielding cancer cells against DNA damage induced by AXL inhibition or SMA68 deficiency.
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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.