ArticleOncotarget2013
Mitochondrial oxidative stress is the Achille's heel of melanoma cells resistant to Braf-mutant inhibitor.
Article in Oncotarget, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
What it found
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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
98 citing papers in PubMed, 176 citations in OpenAlex.
- OCancer cell · 2017Trial
- Cuproptosis in inflammation and cancer: molecular mechanisms and therapeutic targets.Molecular cancer · 2026Review
- Multi-omics classification of acute myeloid leukemia guides drug combinations to overcome Venetoclax resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Metabolic reprogramming in melanoma therapy.Cell death discovery · 2025Review
- Recent Updates on the Efficacy of Mitocans in Photo/Radio-therapy for Targeting Metabolism in Chemo/Radio-resistant Cancers: Nanotherapeutics.Current medicinal chemistry · 2025Review
- Mammalian copper homeostasis: physiological roles and molecular mechanisms.Physiological reviews · 2025Review
- Strategies to combat cancer drug resistance: focus on copper metabolism and cuproptosis.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Exploiting acquired vulnerability to develop novel treatments for cholangiocarcinoma.Cancer cell international · 2024Review
- Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy.Biomarker research · 2024Review
- Cuproptosis in cancer: biological implications and therapeutic opportunities.Cellular & molecular biology letters · 2024Review
- Review
- Modeling Melanoma Heterogeneity In Vitro: Redox, Resistance and Pigmentation Profiles.Antioxidants (Basel, Switzerland) · 2024Article
- Metabolic Profiling to Assess Response to Targeted and Immune Therapy in Melanoma.International journal of molecular sciences · 2024Review
- Augmenting MEK inhibitor efficacy in BRAF wild-type melanoma: synergistic effects of disulfiram combination therapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Cuproptosis and its application in different cancers: an overview.Molecular and cellular biochemistry · 2023Article
- Elesclomol, a copper-transporting therapeutic agent targeting mitochondria: from discovery to its novel applications.Journal of translational medicine · 2023Review
- Skin Cancer Microenvironment: What We Can Learn from Skin Aging?International journal of molecular sciences · 2023Review
- Nrf2 as a Therapeutic Target in the Resistance to Targeted Therapies in Melanoma.Antioxidants (Basel, Switzerland) · 2023Article
- Synthesis and the In Vitro Evaluation of Antitumor Activity of Novel Thiobenzanilides.Molecules (Basel, Switzerland) · 2023Article
- Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vemurafenib/PLX4032, a selective inhibitor of mutant BRAFV600E, constitutes a paradigm shift in melanoma therapy. Unfortunately, acquired resistance, which unavoidably occurs, represents one major limitation to clinical responses. Recent studies have highlighted that vemurafenib activated oxidative metabolism in BRAFV600E melanomas expressing PGC1α. However, the oxidative state of melanoma resistant to BRAF inhibitors is unknown. We established representative in vitro and in vivo models of human melanoma resistant to vemurafenib including primary specimens derived from melanoma patients. Firstly, our study reveals that vemurafenib increased mitochondrial respiration and ROS production in BRAFV600E melanoma cell lines regardless the expression of PGC1α. Secondly, melanoma cells that have acquired resistance to vemurafenib displayed intrinsically high rates of mitochondrial respiration associated with elevated mitochondrial oxidative stress irrespective of the presence of vemurafenib. Thirdly, the elevated ROS level rendered vemurafenib-resistant melanoma cells prone to cell death induced by pro-oxidants including the clinical trial drug, elesclomol. Based on these observations, we propose that the mitochondrial oxidative signature of resistant melanoma constitutes a novel opportunity to overcome resistance to BRAF inhibition.
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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.