ArticleJournal of dental research2021
mTOR Inhibition Ablates Cisplatin-Resistant Salivary Gland Cancer Stem Cells.
Article in Journal of dental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Expression profile of cancer stem cell markers SOX2, OCT4 & NANOG in salivary gland malignancies: A systematic review.The Indian journal of medical research · 2025Pooled it
- Head and neck squamous cell carcinoma: current and emerging therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Signaling pathways as the pivotal regulators of cisplatin resistance in tumor cells through SOX2 upregulation.Medical oncology (Northwood, London, England) · 2025Review
- Cell culture in salivary gland tumor research: molecular insights of pathogenic targets and personalized medicine.Cytotechnology · 2025Review
- Characterization of uniquely tumorigenic cancer stem cells in salivary gland adenoid cystic carcinoma.Frontiers in oral health · 2025Article
- Review
- Nanoparticle co-delivery of carboplatin and PF543 restores platinum sensitivity in ovarian cancer models through inhibiting platinum-induced pro-survival pathway activation.Nanoscale advances · 2024Article
- Targeting cancer stem cells as a strategy for reducing chemotherapy resistance in head and neck cancers.Journal of cancer research and clinical oncology · 2023Review
- Therapeutic inhibition of Bmi-1 ablates chemoresistant cancer stem cells in adenoid cystic carcinoma.Oral oncology · 2023Article
- Signaling pathways in cancer metabolism: mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway.Journal of Zhejiang University. Science. B · 2023Article
- Bmi-1: A master regulator of head and neck cancer stemness.Frontiers in oral health · 2023Review
- p-S6 as a Prognostic Biomarker in Canine Oral Squamous Cell Carcinoma.Biomolecules · 2022Article
- Autophagy regulates the cancer stem cell phenotype of head and neck squamous cell carcinoma through the noncanonical FOXO3/SOX2 axis.Oncogene · 2022Article
- Oral Cancer Stem Cells: Therapeutic Implications and Challenges.Frontiers in oral health · 2021Review
- Cancer stem cells in head and neck cancer.American journal of stem cells · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Patients with advanced salivary gland mucoepidermoid carcinoma (MEC) are treated with surgery and radiotherapy, as current systemic therapies are largely ineffective. As such, current treatment frequently leads to poor long-term survival due to locoregional recurrence or metastases. We have shown that salivary gland cancer stem cells (CSCs) are resistant to platinum-based chemotherapy and drive tumor progression. The purpose of this study was to investigate the effect of therapeutic inhibition of mTOR (mechanistic target of rapamycin) on resistance of CSCs to cisplatin, a prototypic platinum-based chemotherapeutic agent. Viability assays determined the effect of several inhibitors of PI3k/mTOR signaling (e.g., temsirolimus, BKM120, AZD8055, PF4708671) and/or cisplatin on survival of human MEC cells. The impact of mTOR inhibitors and/or cisplatin on MEC stemness was examined with salisphere assays, flow cytometry for ALDH/CD44 (CSC markers for MEC), and Western blots for Bmi-1 expression (marker of stem cell self-renewal). Salivary gland MEC patient-derived xenografts were used to examine the effect of cisplatin and/or temsirolimus on CSCs in vivo. We observed that cisplatin induced mTOR and S6K1 phosphorylation, increased the number and size of MEC salispheres, and induced Bmi-1 expression and the fraction of CSCs in MEC models in vitro. Cisplatin also increased the fraction of CSCs in vivo. In contrast, mTOR inhibition (e.g., temsirolimus) blocked cisplatin-induced Bmi-1 expression and salisphere formation in vitro. Remarkably, temsirolimus slowed down tumor growth and decreased the fraction of CSCs (
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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.