ArticleScience translational medicine2021
Repurposed floxacins targeting RSK4 prevent chemoresistance and metastasis in lung and bladder cancer.
Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
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- Expression of ribosomal S6 kinase 4 in bladder cancer and its correlation with clinicopathological features.Frontiers in oncology · 2026Article
- In silico drug sensitivity predicts subgroup-specific therapeutics in medulloblastoma patients.Scientific reports · 2025Article
- Repurposing antibiotics: A dual-action approach against bacteria-induced cancer.Cancer pathogenesis and therapy · 2025Review
- RiSKs in Computational Modeling of Isoform-Selective RSK Inhibitors.Journal of chemical information and modeling · 2025Review
- Loss of Drosophila ribosomal protein S6 kinase II causes mitochondrial dysfunction and cell death.Disease models & mechanisms · 2025Article
- Repurposing Amiodarone for Bladder Cancer Treatment.Cancer research communications · 2025Article
- RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.Expert opinion on therapeutic targets · 2024Review
- Identification of 5-nitroindazole as a multitargeted inhibitor for CDK and transferase kinase in lung cancer: a multisampling algorithm-based structural study.Molecular diversity · 2024Article
- Change in Tissue Microbiome and Related Human Beta Defensin Levels Induced by Antibiotic Use in Bladder Carcinoma.International journal of molecular sciences · 2024Article
- Updating mRNA variants of the human RSK4 gene and their expression in different stressed situations.Heliyon · 2024Article
- METTL3 drives NSCLC metastasis by enhancing CYP19A1 translation and oestrogen synthesis.Cell & bioscience · 2024Article
- Delineated 3-1-BenCarMethInYlPro-Phosphonic Acid's Adroit Activity against Lung Cancer through Multitargeted Docking, MM\GBSA, QM-DFT and Multiscale Simulations.International journal of molecular sciences · 2024Article
- Therapeutic targeting of p90 ribosomal S6 kinase.Frontiers in cell and developmental biology · 2023Review
- Applications and advancements of CRISPR-Cas in the treatment of lung cancer.Frontiers in cell and developmental biology · 2023Review
- Differential Expression of RSK4 Transcript Isoforms in Cancer and Its Clinical Relevance.International journal of molecular sciences · 2022Article
- Allosteric Hotspots in the Main Protease of SARS-CoV-2.Journal of molecular biology · 2022Article
- Development of new bioactive molecules to treat breast and lung cancer with natural myricetin and its derivatives: A computational and SAR approach.Frontiers in cellular and infection microbiology · 2022Article
- Epigenetic modification and BRAF gene mutation in thyroid carcinoma.Cancer cell international · 2021Review
Corrections and comments
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Authors and funding
43 authors at 18 institutions in 6 countries.
Funding
Abstract
Lung and bladder cancers are mostly incurable because of the early development of drug resistance and metastatic dissemination. Hence, improved therapies that tackle these two processes are urgently needed to improve clinical outcome. We have identified RSK4 as a promoter of drug resistance and metastasis in lung and bladder cancer cells. Silencing this kinase, through either RNA interference or CRISPR, sensitized tumor cells to chemotherapy and hindered metastasis in vitro and in vivo in a tail vein injection model. Drug screening revealed several floxacin antibiotics as potent RSK4 activation inhibitors, and trovafloxacin reproduced all effects of RSK4 silencing in vitro and in/ex vivo using lung cancer xenograft and genetically engineered mouse models and bladder tumor explants. Through x-ray structure determination and Markov transient and Deuterium exchange analyses, we identified the allosteric binding site and revealed how this compound blocks RSK4 kinase activation through binding to an allosteric site and mimicking a kinase autoinhibitory mechanism involving the RSK4's hydrophobic motif. Last, we show that patients undergoing chemotherapy and adhering to prophylactic levofloxacin in the large placebo-controlled randomized phase 3 SIGNIFICANT trial had significantly increased (
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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.