ArticleFrontiers in pharmacology2017
Cisplatin and Pemetrexed Activate AXL and AXL Inhibitor BGB324 Enhances Mesothelioma Cell Death from Chemotherapy.
Article in Frontiers in pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- The Multifaceted Roles of TAM Receptors during Viral Infection.Virologica Sinica · 2021Pooled it
- Metabolic vulnerabilities in pleural mesothelioma.Oncogenesis · 2026Review
- Evaluation of the Role of AXL in Fusion-positive Pediatric Rhabdomyosarcoma Identifies the Small-molecule Inhibitor Bemcentinib (BGB324) as Potent Chemosensitizer.Molecular cancer therapeutics · 2024Article
- Target Therapy in Malignant Pleural Mesothelioma: Hope or Mirage?International journal of molecular sciences · 2023Review
- Bacterial outer membrane vesicle based versatile nanosystem boosts the efferocytosis blockade triggered tumor-specific immunity.Nature communications · 2023Article
- AXL inhibition improves BRAF-targeted treatment in melanoma.Scientific reports · 2022Article
- Review
- Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity.Frontiers in oncology · 2022Article
- Anti-Axl monoclonal antibodies attenuate the migration of MDA-MB-231 breast cancer cells.Oncology letters · 2021Article
- Quinacrine Induces Nucleolar Stress in Treatment-Refractory Ovarian Cancer Cell Lines.Cancers · 2021Article
- Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies.Molecules (Basel, Switzerland) · 2021Review
- Review
- Quinacrine Has Preferential Anticancer Effects on Mesothelioma Cells With Inactivating NF2 Mutations.Frontiers in pharmacology · 2021Article
- hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway.Stem cell research & therapy · 2020Article
- The Drug-Resistance Mechanisms of Five Platinum-Based Antitumor Agents.Frontiers in pharmacology · 2020Review
- Identification of pAKT as a pharmacodynamic marker for MER kinase in human melanoma G361 cells.Biomarker research · 2020Article
- Curcumin-Synthetic Analogs Library Screening by Docking and Quantitative Structure-Activity Relationship Studies for AXL Tyrosine Kinase Inhibition in Cancers.Journal of computational biology : a journal of computational molecular cell biology · 2019Article
- PFKFB3 inhibition reprograms malignant pleural mesothelioma to nutrient stress-induced macropinocytosis and ER stress as independent binary adaptive responses.Cell death & disease · 2019Article
- Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications.Nature communications · 2019Article
- Therapeutic Inhibition of the Receptor Tyrosine Kinase AXL Improves Sensitivity to Platinum and Taxane in Ovarian Cancer.Molecular cancer therapeutics · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
Abstract
Reactive oxygen species (ROS) can promote or inhibit tumorigenesis. In mesothelioma, asbestos exposure to serous membranes induces ROS through iron content and chronic inflammation, and ROS promote cell survival signaling in mesothelioma. Moreover, a current chemotherapy regimen for mesothelioma consisting of a platinum and antifolate agent combination also induce ROS. Mesothelioma is notoriously chemotherapy-resistant, and we propose that ROS induced by cisplatin and pemetrexed may promote cell survival signaling pathways, which ultimately may contribute to chemotherapy resistance. In The Cancer Genome Atlas datasets, we found AXL kinase expression is relatively high in mesothelioma compared to other cancer samples. We showed that ROS induce the phosphorylation of AXL, which was blocked by the selective inhibitor BGB324 in VMC40 and P31 mesothelioma cells. We also showed that cisplatin and pemetrexed induce the phosphorylation of AXL and Akt, which was also blocked by BGB324 as well as by N-acetylcysteine antioxidant. AXL knockdown in these cells enhances sensitivity to cisplatin and pemetrexed. Similarly, AXL inhibitor BGB324 also enhances sensitivity to cisplatin and pemetrexed. Finally, higher synergy was observed when cells were pretreated with BGB324 before adding chemotherapy. These results demonstrate cisplatin and pemetrexed induce ROS that activate AXL, and blocking AXL activation enhances the efficacy of cisplatin and pemetrexed. These results suggest AXL inhibition combined with the current chemotherapy regimen may represent an effective strategy to enhance the efficacy of chemotherapy in mesothelioma. This is the first study, to our knowledge, on chemotherapy-induced activation of AXL and cell survival pathways associated with ROS signaling.
Indexed as
Identifiers
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.