ArticleCancer research2008
A retroinhibition approach reveals a tumor cell-autonomous response to rapamycin in head and neck cancer.
Article in Cancer research, 2008. 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, 46 citations in OpenAlex.
- The effect of the mTOR inhibitor rapamycin on glucoCEST signal in a preclinical model of glioblastoma.Magnetic resonance in medicine · 2019Article
- Genome-wide prediction of synthetic rescue mediators of resistance to targeted and immunotherapy.Molecular systems biology · 2019Article
- mTOR Signaling in Cancer and mTOR Inhibitors in Solid Tumor Targeting Therapy.International journal of molecular sciences · 2019Review
- Non-invasive intravital imaging of head and neck squamous cell carcinomas in live mice.Methods (San Diego, Calif.) · 2017Article
- mTOR, metabolism, and the immune response in HPV-positive head and neck squamous cell cancer.World journal of otorhinolaryngology - head and neck surgery · 2016Review
- A synthetic-lethality RNAi screen reveals an ERK-mTOR co-targeting pro-apoptotic switch in PIK3CA+ oral cancers.Oncotarget · 2016Article
- Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter.Nanoscale · 2016Article
- S-Nitrosoglutathione-mediated STAT3 regulation in efficacy of radiotherapy and cisplatin therapy in head and neck squamous cell carcinoma.Redox biology · 2015Article
- mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations.Journal of the National Cancer Institute · 2014Article
- A role for p38 MAPK in head and neck cancer cell growth and tumor-induced angiogenesis and lymphangiogenesis.Molecular oncology · 2014Article
- Improved clearance during treatment of HPV-positive head and neck cancer through mTOR inhibition.Neoplasia (New York, N.Y.) · 2013Article
- The VHL/HIF axis in clear cell renal carcinoma.Seminars in cancer biology · 2013Review
- Targeting TORC1/2 enhances sensitivity to EGFR inhibitors in head and neck cancer preclinical models.Neoplasia (New York, N.Y.) · 2012Article
- Autophagic action of new targeting agents in head and neck oncology.Cancer biology & therapy · 2012Review
- mTOR as a molecular target in HPV-associated oral and cervical squamous carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Longitudinal imaging studies of tumor microenvironment in mice treated with the mTOR inhibitor rapamycin.PloS one · 2012Article
- Increases in mitochondrial biogenesis impair carcinogenesis at multiple levels.Molecular oncology · 2011Article
- New insights into the biology of renal cell carcinoma.Hematology/oncology clinics of North America · 2011Review
- Treatment of prostate and breast tumors employing mono- and bi-specific antisense oligonucleotides targeting apoptosis inhibitory proteins clusterin and bcl-2.Medical oncology (Northwood, London, England) · 2010Article
- Pharmacological retention of oral mucosa progenitor/stem cells.Journal of dental research · 2009Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Emerging evidence supporting the activation of the Akt-mammalian target of rapamycin (mTOR) signaling network in head and neck squamous cell carcinoma (HNSCC) progression has provided the rationale for exploring the therapeutic potential of inhibiting this pathway for HNSCC treatment. Indeed, rapamycin, a clinically relevant mTOR inhibitor, promotes the rapid regression of HNSCC-tumor xenografts in mice. However, rapamycin does not affect the growth of HNSCC cells in vitro, thus raising the possibility that, as for other cancer types, rapamycin may not target cancer cells directly but may instead act on a component of the tumor microenvironment, such as tumor-associated vasculature. Here, we used a retroinhibition approach to assess the contribution of cancer cell-autonomous actions of rapamycin to its antitumor activity in HNSCC. A rapamycin-resistant form of mTOR (mTOR-RR) was expressed in HNSCC cells while retaining the wild-type (rapamycin-sensitive) mTOR (mTOR-WT) alleles in host-derived endothelial and stromal cells. Expression of mTOR-RR prevented the decrease in phospho-S6 levels caused by rapamycin through mTOR in HNSCC cells but not in stromal cells, and rendered HNSCC xenografts completely resistant to the antitumoral activity of rapamycin. This reverse pharmacology strategy also enabled monitoring the direct consequences of inhibiting mTOR in cancer cells within the complex tumor microenvironment, which revealed that mTOR controls the accumulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and the consequent expression of vascular endothelial growth factor and a glucose transporter, Glut-1, in HNSCC cells. These findings indicate that HNSCC cells are the primary target of rapamycin in vivo, and provide evidence that its antiangiogenic effects may represent a downstream consequence of mTOR inhibition in HNSCC cells.
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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.