ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
mTOR Inhibition Mitigates Enhanced mRNA Translation Associated with the Metastatic Phenotype of Osteosarcoma Cells In Vivo.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches.Biomedicines · 2024Review
- Disrupting YAP1-mediated glutamine metabolism induces synthetic lethality alongside ODC1 inhibition in osteosarcoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Pharmacologic Inhibition of EIF4A Blocks NRF2 Synthesis to Prevent Osteosarcoma Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Review
- Recent and Ongoing Research into Metastatic Osteosarcoma Treatments.International journal of molecular sciences · 2022Review
- Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle.International journal of molecular sciences · 2022Article
- Impact of limb amputation and cisplatin chemotherapy on metastatic progression in mouse models of osteosarcoma.Scientific reports · 2021Article
- Novel role of the dietary flavonoid fisetin in suppressing rRNA biogenesis.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- PTHR1 in osteosarcoma: Specific molecular mechanisms and comprehensive functional perspective.Journal of cellular and molecular medicine · 2021Review
- Osteosarcoma and Metastasis.Frontiers in oncology · 2021Review
- C3AR1 mRNA as a Potential Therapeutic Target Associates With Clinical Outcomes and Tumor Microenvironment in Osteosarcoma.Frontiers in medicine · 2021Article
- Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression.Frontiers in oncology · 2020Review
- [Role of mammalian target of rapamycin activation in menthol-induced expressions of airway inflammation-related factors in human bronchial epithelial cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Tegavivint and the β-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma.Journal of the National Cancer Institute · 2019Article
- Lkb1 deletion in periosteal mesenchymal progenitors induces osteogenic tumors through mTORC1 activation.The Journal of clinical investigation · 2019Article
- Practical Considerations in Studying Metastatic Lung Colonization in Osteosarcoma Using the Pulmonary Metastasis Assay.Journal of visualized experiments : JoVE · 2018Article
- Osteosarcoma: Accelerating Progress Makes for a Hopeful Future.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo successfully metastasize, tumor cells must respond appropriately to biological stressors encountered during metastatic progression. We sought to test the hypothesis that enhanced efficiency of mRNA translation during periods of metastatic stress is required for metastatic competence of osteosarcoma and that this metastasis-specific adaptation is amenable to therapeutic intervention. EXPERIMENTAL
designWe employ novel reporter and proteomic systems that enable tracking of mRNA translation efficiency and output in metastatic osteosarcoma cells as they colonize the lungs. We test the potential to target mRNA translation as an antimetastatic therapeutic strategy through pharmacokinetic studies and preclinical assessment of the prototypic mTOR inhibitor, rapamycin, across multiple models of metastasis.
resultsMetastatic osteosarcoma cells translate mRNA more efficiently than nonmetastatic cells during critical stressful periods of metastatic colonization of the lung. Rapamycin inhibits translational output during periods of metastatic stress, mitigates lung colonization, and prolongs survival. mTOR-inhibiting exposures of rapamycin are achievable in mice using treatment schedules that correspond to human doses well below the MTDs defined in human patients, and as such are very likely to be tolerated over long exposures alone and in combination with other agents.
conclusionsMetastatic competence of osteosarcoma cells is dependent on efficient mRNA translation during stressful periods of metastatic progression, and the mTOR inhibitor, rapamycin, can mitigate this translation and inhibit metastasis in vivo Our data suggest that mTOR pathway inhibitors should be reconsidered in the clinic using rationally designed dosing schedules and clinical metrics related to metastatic progression. Clin Cancer Res; 22(24); 6129-41. ©2016 AACR.
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