ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021
Recurrent Human Papillomavirus-Related Head and Neck Cancer Undergoes Metabolic Reprogramming and Is Driven by Oxidative Phosphorylation.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Targeting metabolic reprogramming in HPV-associated oral squamous cell carcinoma: current advances, challenges, and clinical prospects.Journal of molecular histology · 2026Review
- Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification.Translational cancer research · 2026Article
- Drug-tolerant persister cells in head and neck squamous cell carcinoma: Molecular mechanisms and therapeutic opportunities.Translational oncology · 2026Article
- Serum citrulline as a prognostic marker in patients with oropharyngeal carcinoma treated with chemoradiotherapy.Contemporary oncology (Poznan, Poland) · 2026Article
- PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP.eLife · 2025Article
- MRPL21-PARP1 axis promotes cisplatin resistance in head and neck squamous cell carcinoma by inhibiting autophagy through the PI3K/AKT/mTOR signaling pathway.Journal of experimental & clinical cancer research : CR · 2025Article
- Immunotherapeutic strategies in head and neck cancer: challenges and opportunities.The Journal of clinical investigation · 2025Review
- Article
- Targeting cancer and immune cell metabolism with the complex I inhibitors metformin and IACS-010759.Molecular oncology · 2024Review
- Prognosis to Radiation Unlocked: How Hypoxia Methylome May Hold the Key in HNSCC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Crosstalk between oxidative phosphorylation and immune escape in cancer: a new concept of therapeutic targets selection.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Dynamics of oral human papillomavirus infection in healthy population and head and neck cancer.Cancer medicine · 2023Review
- The role of cancer cell bioenergetics in dormancy and drug resistance.Cancer metastasis reviews · 2023Review
- Association of mitochondrial homeostasis and dynamic balance with malignant biological behaviors of gastrointestinal cancer.Journal of translational medicine · 2023Review
- TSPO is a potential independent prognostic factor associated with cellular respiration and p16 in head and neck squamous cell carcinoma.Frontiers in oncology · 2023Article
- HPV E6 regulates therapy responses in oropharyngeal cancer by repressing the PGC-1α/ERRα axis.JCI insight · 2022Article
- Metabolic Adaptation-Mediated Cancer Survival and Progression in Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Review
- Repurposing Ceritinib Induces DNA Damage and Enhances PARP Inhibitor Responses in High-Grade Serous Ovarian Carcinoma.Cancer research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeHuman papillomavirus (HPV) infection drives the development of some head and neck squamous cell carcinomas (HNSCC). This disease is rapidly increasing in incidence worldwide. Although these tumors are sensitive to treatment, approximately 10% of patients fail therapy. However, the mechanisms that underlie treatment failure remain unclear. EXPERIMENTAL
designWe performed RNA sequencing (RNA-seq) on tissues from matched primary- (pHNSCC) and metachronous-recurrent cancers (rHNSCC) to identify transcriptional differences to gain mechanistic insight into the evolutionary adaptations of metachronous-recurrent tumors. We used HPV-related HNSCC cells lines to investigate the effect of (i) NRF2 overexpression on growth
resultsThe OXPHOS pathway is enriched in recurrent HPV-associated HNSCC and may contribute to treatment failure. NRF2-enriched HNSCC samples from The Cancer Genome Atlas (TCGA) with enrichment in OXPHOS, fatty-acid metabolism, Myc, Mtor, reactive oxygen species (ROS), and glycolytic signaling networks exhibited worse survival. HPV-positive HNSCC cells demonstrated sensitivity to the OXPHOS inhibitor, in a NRF2-dependent manner. Further, using murine xenograft models, we identified NRF2 as a driver of tumor growth. Mechanistically, NRF2 drives ROS and mitochondrial respiration, and NRF2 is a critical regulator of redox homeostasis that can be crippled by disruption of OXPHOS. NRF2 also mediated cisplatin sensitivity in endogenously overexpressing primary HPV-related HNSCC cells.
conclusionsThese results unveil a paradigm-shifting translational target harnessing NRF2-mediated metabolic reprogramming in HPV-related HNSCC.
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