ArticleCancer research2011
Reduced VEGF production, angiogenesis, and vascular regrowth contribute to the antitumor properties of dual mTORC1/mTORC2 inhibitors.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
What it found
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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.
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Who cites it
62 citing papers in PubMed, 91 citations in OpenAlex.
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- Vertical pathway inhibition of receptor tyrosine kinases and BAD with synergistic efficacy in triple negative breast cancer.NPJ precision oncology · 2024Article
- D-2-hydroxyglutarate regulates human brain vascular endothelial cell proliferation and barrier function.Journal of neuropathology and experimental neurology · 2023Article
- Towards a Unified Approach in Autoimmune Fibrotic Signalling Pathways.International journal of molecular sciences · 2023Review
- Research progress on the mechanism of angiogenesis in wound repair and regeneration.Frontiers in physiology · 2023Review
- A zebrafish HCT116 xenograft model to predict anandamide outcomes on colorectal cancer.Cell death & disease · 2022Article
- High-throughput screen to identify compounds that prevent or target telomere loss in human cancer cells.NAR cancer · 2022Article
- Phenotypic Screening Using High-Content Imaging to Identify Lysosomal pH Modulators in a Neuronal Cell Model.ACS chemical neuroscience · 2022Article
- Establishment of childhood hepatoblastoma xenografts and evaluation of the anti-tumour effects of anlotinib, oxaliplatin and sorafenib.Pediatric surgery international · 2022Article
- An mTOR and VEGFR inhibitor combination arrests a doxorubicin resistant lung metastatic osteosarcoma in a PDOX mouse model.Scientific reports · 2021Article
- Article
- Naringin inhibits colorectal cancer cell growth by repressing the PI3K/AKT/mTOR signaling pathway.Experimental and therapeutic medicine · 2020Article
- Angiocrine endothelium: from physiology to cancer.Journal of translational medicine · 2020Review
- MicroRNA-200c affects bladder cancer angiogenesis by regulating the Akt2/mTOR/HIF-1 axis.Translational cancer research · 2019Article
- ETV7 is an essential component of a rapamycin-insensitive mTOR complex in cancer.Science advances · 2018Article
- Alterations of mTOR signaling impact metabolic stress resistance in colorectal carcinomas with BRAF and KRAS mutations.Scientific reports · 2018Article
- Article
- Monitoring response to anti-angiogenic mTOR inhibitor therapy in vivo usingEJNMMI research · 2017Article
- Evolving Significance and Future Relevance of Anti-Angiogenic Activity of mTOR Inhibitors in Cancer Therapy.Cancers · 2017Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The mammalian target of rapamycin (mTOR) pathway is implicated widely in cancer pathophysiology. Dual inhibition of the mTOR kinase complexes mTORC1 and mTORC2 decreases tumor xenograft growth in vivo and VEGF secretion in vitro, but the relationship between these two effects are unclear. In this study, we examined the effects of mTORC1/2 dual inhibition on VEGF production, tumor angiogenesis, vascular regression, and vascular regrowth, and we compared the effects of dual inhibition to mTORC1 inhibition alone. ATP-competitive inhibitors OSI-027 and OXA-01 targeted both mTORC1 and mTORC2 signaling in vitro and in vivo, unlike rapamycin that only inhibited mTORC1 signaling. OXA-01 reduced VEGF production in tumors in a manner associated with decreased vessel sprouting but little vascular regression. In contrast, rapamycin exerted less effect on tumoral production of VEGF. Treatment with the selective VEGFR inhibitor OSI-930 reduced vessel sprouting and caused substantial vascular regression in tumors. However, following discontinuation of OSI-930 administration tumor regrowth could be slowed by OXA-01 treatment. Combining dual inhibitors of mTORC1 and mTORC2 with a VEGFR2 inhibitor decreased tumor growth more than either inhibitor alone. Together, these results indicate that dual inhibition of mTORC1/2 exerts antiangiogenic and antitumoral effects that are even more efficacious when combined with a VEGFR antagonist.
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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.