ArticleMolecular cancer therapeutics2011
Interpreting mammalian target of rapamycin and cell growth inhibition in a genetically engineered mouse model of Nf1-deficient astrocytes.
Article in Molecular cancer therapeutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Rapamycin Partially Reverts Cavernoma Endothelial Cell Phenotype and, When Combined With Lapatinib, Ameliorates Chronic Lesions.Journal of cellular and molecular medicine · 2026Article
- NF1 mutation-driven neuronal hyperexcitability sets a threshold for tumorigenesis and therapeutic targeting of murine optic glioma.Neuro-oncology · 2024Article
- PROX1, a Key Mediator of the Anti-Proliferative Effect of Rapamycin on Hepatocellular Carcinoma Cells.Cells · 2022Article
- Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of Autophagy and Immune Response.Biomedicines · 2021Article
- Implications of new understandings of gliomas in children and adults with NF1: report of a consensus conference.Neuro-oncology · 2020Article
- mGluR5 Contribution to Neuropathology in Alzheimer Mice Is Disease Stage-Dependent.ACS pharmacology & translational science · 2020Article
- Mechanistic target of rapamycin (mTOR) implicated in plasticity of the reproductive axis during social status transitions.General and comparative endocrinology · 2019Article
- Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice.Molecular brain · 2019Article
- A novel fibroblast activation inhibitor attenuates left ventricular remodeling and preserves cardiac function in heart failure.American journal of physiology. Heart and circulatory physiology · 2018Article
- Optic Pathway Gliomas in Neurofibromatosis Type 1.Journal of child neurology · 2018Review
- Low-dose rapamycin extends lifespan in a mouse model of mtDNA depletion syndrome.Human molecular genetics · 2017Article
- Inhibition of mTOR signaling Confers Protection against Cerebral Ischemic Injury in Acute Hyperglycemic Rats.International journal of biological sciences · 2017Article
- Neurofibromatosis-1 regulation of neural stem cell proliferation and multilineage differentiation operates through distinct RAS effector pathways.Genes & development · 2015Article
- RASopathies: unraveling mechanisms with animal models.Disease models & mechanisms · 2015Review
- The mTOR signaling pathway as a treatment target for intracranial neoplasms.Neuro-oncology · 2015Review
- mTOR signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Preclinical evaluation of the combination of mTOR and proteasome inhibitors with radiotherapy in malignant peripheral nerve sheath tumors.Journal of neuro-oncology · 2014Article
- Rapamycin delays salivary gland atrophy following ductal ligation.Cell death & disease · 2014Article
- Rapamycin extends life and health in C57BL/6 mice.The journals of gerontology. Series A, Biological sciences and medical sciences · 2014Article
- Potential for treatment of severe autism in tuberous sclerosis complex.World journal of clinical pediatrics · 2013Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The identification of mammalian target of rapamycin (mTOR) as a major mediator of neurofibromatosis-1 (NF1) tumor growth has led to the initiation of clinical trials using rapamycin analogs. Previous studies from our laboratory have shown that durable responses to rapamycin treatment in a genetically engineered mouse model of Nf1 optic glioma require 20 mg/kg/day, whereas only transient tumor growth suppression was observed with 5 mg/kg/day rapamycin despite complete silencing of ribosomal S6 activity. To gain clinically relevant insights into the mechanism underlying this dose-dependent effect, we used Nf1-deficient glial cells in vitro and in vivo. First, there was an exponential relationship between blood and brain rapamycin levels. Second, we show that currently used biomarkers of mTOR pathway inhibition (phospho-S6, phospho-4EBP1, phospho-STAT3, and Jagged-1 levels) and tumor proliferation (Ki67) do not accurately reflect mTOR target inhibition or Nf1-deficient glial growth suppression. Third, the incomplete suppression of Nf1-deficient glial cell proliferation in vivo following 5 mg/kg/day rapamycin treatment reflects mTOR-mediated AKT activation, such that combined 5 mg/kg/day rapamycin and PI3-kinase (PI3K) inhibition or dual PI3K/mTOR inhibition recapitulates the growth suppressive effects of 20 mg/kg/day rapamycin. These new findings argue for the identification of more accurate biomarkers for rapamycin treatment response and provide reference preclinical data for comparing human rapamycin levels with target effects in the brain.
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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.