ArticleBritish journal of cancer2023
Evolution of cisplatin resistance through coordinated metabolic reprogramming of the cellular reductive state.
Article in British journal of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- The SMAC-mimetic xevinapant differentially enhances cisplatin and immune checkpoint blockade efficacy in high-risk HPV-positive tumors.Translational oncology · 2026Article
- Metabolic Reprogramming in Oral Cancer: A Narrative Review of Therapeutic Perspectives with Emphasis on Dichloroacetate.Current issues in molecular biology · 2026Review
- NOTCH1 acts as a tumor suppressor that induces early differentiation in head and neck cancer.JCI insight · 2026Article
- Targeted suppression of SPP1 inhibits tumor invasion and metastasis in NRF2 hyperactivated cisplatin resistant HNSCC.Journal of translational medicine · 2026Article
- The controversial role of metabolic reprogramming in anti-tumor therapy resistance.Discover oncology · 2026Review
- Article
- Bypassing cisplatin resistance in Nrf2 hyperactivated head and neck cancer through effective PI3Kinase targeting.British journal of cancer · 2025Article
- From Carcinogenesis to Drug Resistance: The Multifaceted Role of Oxidative Stress in Head and Neck Cancer.Cancers · 2025Review
- Cisplatin-induced genetic alterations in KEAP1 promote therapeutic resistance in head and neck squamous cell carcinoma.Redox biology · 2025Article
- Senataxin regulates cisplatin resistance through an R-loop-mediated mechanism in HPV-associated head and neck cancer.iScience · 2025Article
- Polo-like kinase 1 inactivation enhances PI3K inhibition-mediated apoptosis of NOTCH1-mutant head and neck squamous cell carcinoma.Cancer letters · 2025Article
- Acquired resistance in cancer: towards targeted therapeutic strategies.Nature reviews. Cancer · 2025Review
- Targeting Endoplasmic Reticulum Stress by Natural and Chemical Compounds Ameliorates Cisplatin-Induced Nephrotoxicity: A Review.Biological trace element research · 2025Review
- Tobacco smoke exposure is a driver of altered oxidative stress response and immunity in head and neck cancer.Journal of translational medicine · 2025Article
- Reliable RNA-seq analysis from FFPE specimens as a means to accelerate cancer-related health disparities research.PloS one · 2025Article
- Massive parallel sequencing of head and neck conventional squamous cell carcinomas: A comprehensive review.Virchows Archiv : an international journal of pathology · 2024Review
- First-in-Human Hyperpolarized MRI for Tumor Metabolism in HNSCC.JAMA otolaryngology-- head & neck surgery · 2024Article
- Cancer metabolic reprogramming and precision medicine-current perspective.Frontiers in pharmacology · 2024Review
- Machine learning driven index of tumor multinucleation correlates with survival and suppressed anti-tumor immunity in head and neck squamous cell carcinoma patients.Oral oncology · 2023Article
Corrections and comments
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Authors and funding
35 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundCisplatin (CDDP) is a mainstay treatment for advanced head and neck squamous cell carcinomas (HNSCC) despite a high frequency of innate and acquired resistance. We hypothesised that tumours acquire CDDP resistance through an enhanced reductive state dependent on metabolic rewiring.
methodsTo validate this model and understand how an adaptive metabolic programme might be imprinted, we performed an integrated analysis of CDDP-resistant HNSCC clones from multiple genomic backgrounds by whole-exome sequencing, RNA-seq, mass spectrometry, steady state and flux metabolomics.
resultsInactivating KEAP1 mutations or reductions in KEAP1 RNA correlated with Nrf2 activation in CDDP-resistant cells, which functionally contributed to resistance. Proteomics identified elevation of downstream Nrf2 targets and the enrichment of enzymes involved in generation of biomass and reducing equivalents, metabolism of glucose, glutathione, NAD(P), and oxoacids. This was accompanied by biochemical and metabolic evidence of an enhanced reductive state dependent on coordinated glucose and glutamine catabolism, associated with reduced energy production and proliferation, despite normal mitochondrial structure and function.
conclusionsOur analysis identified coordinated metabolic changes associated with CDDP resistance that may provide new therapeutic avenues through targeting of these convergent pathways.
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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.