ArticleCancer research2014
Loss of NF1 in cutaneous melanoma is associated with RAS activation and MEK dependence.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
191 citing papers in PubMed, 308 citations in OpenAlex.
- Response Rate and Molecular Correlates to Encorafenib and Binimetinib in BRAF-V600E Mutant High-Grade Glioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Efficacy and safety of trametinib in Japanese patients with advanced biliary tract cancers refractory to gemcitabine.Cancer science · 2018Trial
- Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.Journal of the National Cancer Institute · 2017Trial
- Trial
- International Dermoscopy Society consensus recommendations for the management of lentigo maligna.Journal of the European Academy of Dermatology and Venereology : JEADV · 2026Review
- Genotype-driven tumor ecosystems drive immune evasion and immunotherapy resistance in melanoma.Molecular cancer · 2026Article
- Targeting MAPK Pathways in Skin, Thyroid, and Pancreatic Cancer: A Perspective on Synthetic Inhibitors and Natural Modulators.Advanced biology · 2026Review
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Metastatic Testicular Germ Cell Tumor in a Patient With Neurofibromatosis Type 1: Treatment With Trametinib Based onIJU case reports · 2026Article
- Characterizing the Mutational Landscape of In-Transit Melanoma Metastases.Pigment cell & melanoma research · 2026Article
- Review
- Advantages of MelArray over Oncomine Focus Assay for Mutation Analysis in Melanoma.Medicina (Kaunas, Lithuania) · 2026Article
- Surgical Management of Stage IV Melanoma: Clinical, Molecular, and Therapeutic Considerations.International journal of molecular sciences · 2026Review
- Systemic treatment for a young patient with stage IV melanoma: A case report.Oncology letters · 2026Article
- Redundancy in Growth Factor Receptor Signaling in Adult Astrocytoma Resistance to Small-Molecule Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2026Review
- Dacarbazine as a Positive Control in Melanoma Cell Lines (A375, SK-MEL-103, 1205Lu) and a Human Ex Vivo Skin Model.Advanced biology · 2026Article
- Autophagy and mitophagy in dermatological disease: a comprehensive review from molecular pathways to therapeutic frontiers.Biology direct · 2025Review
- Selective inhibition of BRAF and CRAF sensitizes NF1-deficient malignant peripheral nerve sheath tumors to MEK inhibitors.Molecular medicine (Cambridge, Mass.) · 2025Article
- NF1 Loss Promotes EGFR Activation and Confers Sensitivity to EGFR Inhibition in NF1-Mutant Melanoma.Cancer research · 2025Article
- Review
131 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
19 authors at 4 institutions in 1 country.
Funding
Abstract
Melanoma is a disease characterized by lesions that activate ERK. Although 70% of cutaneous melanomas harbor activating mutations in the BRAF and NRAS genes, the alterations that drive tumor progression in the remaining 30% are largely undefined. Vemurafenib, a selective inhibitor of RAF kinases, has clinical utility restricted to BRAF-mutant tumors. MEK inhibitors, which have shown clinical activity in NRAS-mutant melanoma, may be effective in other ERK pathway-dependent settings. Here, we investigated a panel of melanoma cell lines wild type for BRAF and NRAS to determine the genetic alteration driving their transformation and their dependence on ERK signaling in order to elucidate a candidate set for MEK inhibitor treatment. A cohort of the BRAF/RAS wild type cell lines with high levels of RAS-GTP had loss of NF1, a RAS GTPase activating protein. In these cell lines, the MEK inhibitor PD0325901 inhibited ERK phosphorylation, but also relieved feedback inhibition of RAS, resulting in induction of pMEK and a rapid rebound in ERK signaling. In contrast, the MEK inhibitor trametinib impaired the adaptive response of cells to ERK inhibition, leading to sustained suppression of ERK signaling and significant antitumor effects. Notably, alterations in NF1 frequently co-occurred with RAS and BRAF alterations in melanoma. In the setting of BRAF(V600E), NF1 loss abrogated negative feedback on RAS activation, resulting in elevated activation of RAS-GTP and resistance to RAF, but not MEK, inhibitors. We conclude that loss of NF1 is common in cutaneous melanoma and is associated with RAS activation, MEK-dependence, and resistance to RAF inhibition.
Indexed as
Identifiers
What OpenQuestion holds
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.