ArticleCancer discovery2014
A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors.
Article in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 336 papers.
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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.
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Who cites it
336 citing papers in PubMed, 534 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- Genetic Drivers of Sensitivity or Resistance to RAS(ON) Multiselective Inhibitors in NRAS-Mutated Melanoma.Cancer research · 2026Article
- Metabolic buffering restricts phenotype switching in melanoma.The EMBO journal · 2026Article
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- MAPK Inhibitor-Tolerant Persister Cells in Melanoma: Mechanisms and Therapeutic Vulnerabilities.Cancer science · 2026Review
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Regulated cell death plasticity in cancer: thresholds, reversibility, and therapeutic failure.Journal of translational medicine · 2026Review
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- MITF Gain-of-Function Mutation in Metastatic Prostate Cancer: A Rare Finding With Potential Therapeutic Significance.Cancer reports (Hoboken, N.J.) · 2026Article
- A MAFG~MITF complex drives melanoma phenotype switching and progression.Nature communications · 2026Article
- FGFR1 but not S6K1/2 drives intrinsic BRAF inhibitor resistance in melanoma.Cell death discovery · 2026Article
- The neural crest-associated gene ERRFI1 is involved in melanoma progression and resistance toward targeted therapy.Molecular oncology · 2026Article
- Androgen receptor and fatty acid oxidation cooperate in ferroptosis evasion in BRAFi resistant melanoma.Cell death & disease · 2026Article
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- Article
- Elucidating the role of medicinal plants in melanoma treatment: a review on metastatic progression and phytochemical intervention.Frontiers in pharmacology · 2026Review
- ATAD2 drives melanoma growth and progression and inhibits ferroptosis.EMBO reports · 2026Article
- MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma.Cell reports · 2025Article
- Targeting FZD6 creates therapeutically actionable vulnerabilities for advanced prostate cancer.Oncogene · 2025Article
- Receptor tyrosine kinase inhibitor tivozanib regulates cell state plasticity and restores MITF dependency in BRAF wild-type melanoma.Acta pharmacologica Sinica · 2025Article
276 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledMost melanomas harbor oncogenic BRAF(V600) mutations, which constitutively activate the MAPK pathway. Although MAPK pathway inhibitors show clinical benefit in BRAF(V600)-mutant melanoma, it remains incompletely understood why 10% to 20% of patients fail to respond. Here, we show that RAF inhibitor-sensitive and inhibitor-resistant BRAF(V600)-mutant melanomas display distinct transcriptional profiles. Whereas most drug-sensitive cell lines and patient biopsies showed high expression and activity of the melanocytic lineage transcription factor MITF, intrinsically resistant cell lines and biopsies displayed low MITF expression but higher levels of NF-κB signaling and the receptor tyrosine kinase AXL. In vitro, these MITF-low/NF-κB-high melanomas were resistant to inhibition of RAF and MEK, singly or in combination, and ERK. Moreover, in cell lines, NF-κB activation antagonized MITF expression and induced both resistance marker genes and drug resistance. Thus, distinct cell states characterized by MITF or NF-κB activity may influence intrinsic resistance to MAPK pathway inhibitors in BRAF(V600)-mutant melanoma. SIGNIFICANCE: Although most BRAF(V600)-mutant melanomas are sensitive to RAF and/or MEK inhibitors, a subset fails to respond to such treatment. This study characterizes a transcriptional cell state distinction linked to MITF and NF-κB that may modulate intrinsic sensitivity of melanomas to MAPK pathway inhibitors.
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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.