ArticleCancers2020
BRAF Mutant Melanoma Adjusts to BRAF/MEK Inhibitors via Dependence on Increased Antioxidant SOD2 and Increased Reactive Oxygen Species Levels.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 30 citations in OpenAlex.
- Proteomic Signatures of Vemurafenib Resistance in Canine Urothelial Carcinoma Harboring the BRAFV595E Mutation.Journal of proteome research · 2026Article
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Comparative Proteomic Analysis of the Secretome of Control and BRAF/MEK Inhibitor-Resistant Melanoma Cells.Journal of proteome research · 2026Article
- Onconase Induces Apoptosis in Dabrafenib-Resistant Melanoma Cell Lines Through Dysregulation of ROS Homeostasis, Antioxidant Protein Expression, and Mitochondrial Dynamics.International journal of molecular sciences · 2026Article
- TET2 downregulation limits oxidative stress-induced cytotoxicity of high dose ascorbate in dabrafenib-resistant melanoma cells.Cancer drug resistance (Alhambra, Calif.) · 2026Article
- Prodelphinidin from purple sweet potato induces apoptosis in human triple-negative breast cancer cells via ROS-mediated ER stress activation.Medical oncology (Northwood, London, England) · 2025Article
- Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.Cancer treatment reviews · 2024Review
- Augmenting MEK inhibitor efficacy in BRAF wild-type melanoma: synergistic effects of disulfiram combination therapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Curcumin Enhances the Anticancer Effects of Binimetinib on Melanoma Cells by Inducing Mitochondrial Dysfunction and Cell Apoptosis with Necroptosis.Annals of dermatology · 2023Article
- Reactive Oxygen Species Regulation of Chemoresistance and Metastatic Capacity of Melanoma: Role of the Cancer Stem Cell Marker CD271.Biomedicines · 2023Article
- Combined PARP inhibitors and small molecular inhibitors in solid tumor treatment (Review).International journal of oncology · 2023Review
- Targeting mitochondrial metabolism for metastatic cancer therapy.Molecular carcinogenesis · 2022Review
- Trehalose Attenuates Oxidative Stress and Endoplasmic Reticulum Stress-Mediated Apoptosis in IPEC-J2 Cells Subjected to Heat Stress.Animals : an open access journal from MDPI · 2022Article
- Low Doses of Celecoxib Might Promote Phenotype Switching in Cutaneous Melanoma Treated with Dabrafenib-Preliminary Study.Journal of clinical medicine · 2022Article
- Dyslipidemia in Children Treated with a BRAF Inhibitor for Low-Grade Gliomas: A New Side Effect?Cancers · 2022Article
- Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges.Cancer discovery · 2022Article
- Review
- Redox-Related Proteins in Melanoma Progression.Antioxidants (Basel, Switzerland) · 2022Article
- Evaluation of Bioactive Properties of Lipophilic Fractions of Edible and Non-Edible Parts ofPharmaceuticals (Basel, Switzerland) · 2022Article
- Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B-Rapidly Accelerated Fibrosarcoma (BRAF) mutations are found in about 50% of melanoma patients. Treatment with Food and Drug Administration (FDA)-approved BRAF and MAP/ERK kinase (MEK) inhibitors has improved progression free and overall survival of patients with BRAF mutant melanoma. However, all responders develop resistance typically within 1 year of treatment with these inhibitors. Evidence indicates that reactive oxygen species (ROS) levels are elevated after BRAF pathway inhibition treatment. We aim to decipher the role of mitochondrial antioxidant proteins relative to ROS levels and BRAF pathway inhibitor resistance. We observed BRAF mutant melanoma cells treated with the combination of a MEK inhibitor (trametinib) and a BRAF inhibitor (dabrafenib), exhibited elevated ROS levels, both in in vitro and in vivo melanoma models. We next generated trametinib- and dabrafenib-resistant (TDR) cells and found increased ROS levels after acquisition of resistance. An immunofluorescence experiment showed an increase of DNA damage in TDR cell lines. Furthermore, we observed that TDR cells increased superoxide dismutase 2 (SOD2), an antioxidant, at both mRNA and protein levels, with the upregulation of the transcription factor Nuclear Factor (NF)-κB. Knockdown of SOD2 significantly reduced the growth of BRAF pathway inhibitor-resistant cells. In addition, the results indicate that TDR cells can be re-sensitized to BRAF pathway inhibitors by the ROS scavenger, N-Acetyl Cysteine (NAC). Overall, these data indicate that BRAF pathway inhibitor-resistant cells can compensate for elevated ROS via increased expression of the antioxidant SOD2.
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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.