ArticleNeoplasia (New York, N.Y.)2013
Improved clearance during treatment of HPV-positive head and neck cancer through mTOR inhibition.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Activation of the cGAS-STING pathway contributes to cancer-related fatigue in a murine model of head and neck cancer.Brain, behavior, and immunity · 2026Article
- Antagonism of β-klotho signaling by peptide 19 impairs wheel running in male mice and potentiates the cisplatin-induced decrease in wheel running.Frontiers in pharmacology · 2026Article
- Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16Exploration of targeted anti-tumor therapy · 2026Article
- Activation of the cGAS-STING pathway contributes to cancer-related fatigue in a murine model of head and neck cancer.bioRxiv : the preprint server for biology · 2025Article
- Exploring the antiproliferative effect of PI3K/Akt/mTOR pathway and CDK4/6 inhibitors in human papillomavirus‑positive and ‑negative head and neck squamous cell carcinoma cell lines.International journal of oncology · 2025Article
- Immune-metabolic crosstalk in HNSCC: mechanisms and therapeutic opportunities.Frontiers in oncology · 2025Review
- Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.Cell reports. Medicine · 2024Article
- Article
- Harnessing glucose metabolism with nanomedicine for cancer treatment.Theranostics · 2024Review
- Targeted therapy for head and neck cancer: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
- Everolimus, an mTORC1/2 inhibitor, in ART-suppressed individuals who received solid organ transplantation: A prospective study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.BMC cancer · 2021Article
- Rapid development of HIV elite control in a patient with acute infection.BMC infectious diseases · 2019Article
- Propranolol Promotes Glucose Dependence and Synergizes with Dichloroacetate for Anti-Cancer Activity in HNSCC.Cancers · 2018Article
- Mouse Models for Studying Oral Cancer: Impact in the Era of Cancer Immunotherapy.Journal of dental research · 2018Review
- Molecular and serologic markers of HPV 16 infection are associated with local recurrence in patients with oral cavity squamous cell carcinoma.Oncotarget · 2017Article
- Induction of dormancy in hypoxic human papillomavirus-positive cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Untangling the most probable role for vitamin DDermato-endocrinology · 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
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) incidence is increasing at a near epidemic rate. We investigated whether the mammalian (or mechanistic) target of rapamycin (mTOR) inhibitor, rapamycin, can be used as a concurrent agent to standard-of-care cisplatin/radiation therapy (CRT) to attenuate tumor lactate production, thus enhancing CRT-induced immune-mediated clearance of this antigenic tumor type. A C57Bl/6-derived mouse oropharyngeal epithelial cell line retrovirally transduced with HPV type 16 E6/E7 and human squamous cell carcinoma cell lines were evaluated for their response to rapamycin in vitro with proliferation assays, Western blots, and lactate assays. Clonogenic assays and a preclinical mouse model were used to assess rapamycin as a concurrent agent to CRT. The potential of rapamycin to enhance immune response through lactate attenuation was assessed using quantitative tumor lactate bioluminescence and assessment of cell-mediated immunity using E6/E7-vaccinated mouse splenocytes. Rapamycin alone inhibited mTOR signaling of all cancer cell lines tested in vitro and in vivo. Furthermore, rapamycin administered alone significantly prolonged survival in vivo but did not result in any long-term cures. Given concurrently, CRT/rapamycin significantly enhanced direct cell killing in clonogenic assays and prolonged survival in immunocompromised mice. However, in immunocompetent mice, concurrent CRT/rapamycin increased long-term cures by 21%. Preliminary findings suggest that improved survival involves increased cell killing and enhanced immune-mediated clearance in part due to decreased lactate production. The results may provide rationale for the clinical evaluation of mTOR inhibitors concurrent with standard-of-care CRT for treatment of HPV-positive HNSCC.
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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.