ArticleOncogene2015
A stress-induced early innate response causes multidrug tolerance in melanoma.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 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.
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Who cites it
88 citing papers in PubMed.
- Loss ofJCO precision oncology · 2021Trial
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- Predicting targeted- and immunotherapeutic response outcomes in melanoma with single-cell Raman spectroscopy and AI.bioRxiv : the preprint server for biology · 2026Article
- The role of KDM5B in creating synthetic vulnerabilities in combination with radiotherapy in melanoma cells.Cell communication and signaling : CCS · 2026Article
- Adaptive drug resistance in melanoma is characterised by lipidome remodelling while maintaining cell membrane biophysical properties.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models.Nature communications · 2025Article
- Targeting Drug-Tolerant Persister Cancer Cells: Can Nanomaterial-Based Strategies Be Helpful for Anti-DTP Therapies?Pharmaceutics · 2025Review
- Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- Deciphering genetic and nongenetic factors underlying tumour dormancy: insights from multiomics analysis of two syngeneic MRD models of melanoma and leukemia.Biological research · 2024Article
- Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer.Cancer research communications · 2024Article
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Review
- Purinergic CaCancers · 2024Article
- Purinergic CabioRxiv : the preprint server for biology · 2024Article
- Clonal differences underlie variable responses to sequential and prolonged treatment.Cell systems · 2024Article
- Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.Cancer metastasis reviews · 2024Review
- Real-Time Cell Cycle Imaging in a 3D Cell Culture Model of Melanoma, Quantitative Analysis, Optical Clearing, and Mathematical Modeling.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Cancer Stem Cells: Current Challenges and Future Perspectives.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
17 authors.
Funding
Abstract
Acquired drug resistance constitutes a major challenge for effective cancer therapies with melanoma being no exception. The dynamics leading to permanent resistance are poorly understood but are important to design better treatments. Here we show that drug exposure, hypoxia or nutrient starvation leads to an early innate cell response in melanoma cells resulting in multidrug resistance, termed induced drug-tolerant cells (IDTCs). Transition into the IDTC state seems to be an inherent stress reaction for survival toward unfavorable environmental conditions or drug exposure. The response comprises chromatin remodeling, activation of signaling cascades and markers implicated in cancer stemness with higher angiogenic potential and tumorigenicity. These changes are characterized by a common increase in CD271 expression concomitantly with loss of differentiation markers such as melan-A and tyrosinase, enhanced aldehyde dehydrogenase (ALDH) activity and upregulation of histone demethylases. Accordingly, IDTCs show a loss of H3K4me3, H3K27me3 and gain of H3K9me3 suggesting activation and repression of differential genes. Drug holidays at the IDTC state allow for reversion into parental cells re-sensitizing them to the drug they were primarily exposed to. However, upon continuous drug exposure IDTCs eventually transform into permanent and irreversible drug-resistant cells. Knockdown of CD271 or KDM5B decreases transition into the IDTC state substantially but does not prevent it. Targeting IDTCs would be crucial for sustainable disease management and prevention of acquired drug resistance.
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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.