Trial reportThe New England journal of medicine2012
RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors.
Trial report in The New England journal of medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 456 papers, 2 of them syntheses that pooled it.
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.
A Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX4032 in Patients With Solid Tumors
An Open-label Multicenter Study on the Efficacy of Continuous Oral Dosing of Vemurafenib on Tumour Response in Previously Treated Patients With Metastatic Melanoma
A Multi-center, Open-label, Study to Investigate the Pharmacokinetic Interaction of RO5185426 With a "Cocktail" of Five Probe Drugs for CYP450 Dependent Metabolism in Patients With Previously Treated and Untreated Metastatic Melanoma
BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine
A Phase 1, Open-Label Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy Study of Topically Administered LUT017 Gel for Cutaneous Wound Healing
A Phase 1, Open-Label Clinical Trial to Assess the Safety, Tolerability, and Preliminary Efficacy Study of a Single Dose of Topically Administered LUT017 Gel for Cutaneous Wound Healing in Volunteers With Healthy Skin
Who cites it
456 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,015 citations in OpenAlex.
- Network indirect comparison of 3 BRAF + MEK inhibitors for the treatment of advanced BRAF mutated melanoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Pooled it
- Clinical outcomes of BRAF plus MEK inhibition in melanoma: A meta-analysis and systematic review.Cancer medicine · 2019Pooled it
- Dabrafenib, trametinib and pembrolizumab or placebo in BRAF-mutant melanoma.Nature medicine · 2019Trial
- Dual MEK/AKT inhibition with trametinib and GSK2141795 does not yield clinical benefit in metastatic NRAS-mutant and wild-type melanoma.Pigment cell & melanoma research · 2018Trial
- Response to RAF/MEK/ERK Inhibitors in Patients with RAS-Altered and Wild-Type Tumors.Journal of immunotherapy and precision oncology · 2026Article
- Cutaneous Adverse Drug Reactions Associated With BRAF and MEK Inhibitors: A Real-World Analysis of WHO Pharmacovigilance Data.Clinical pharmacology and therapeutics · 2026Article
- Oncogenic signaling pathways in ameloblastoma and their implications for precision based therapy.Discover oncology · 2026Review
- Review
- Erdheim-Chester disease associated with myeloid neoplasm: Clinical features, molecular landscape, and treatment outcomes.HemaSphere · 2026Article
- Tumour promotion through the lens of evolution.Nature · 2026Review
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Wearable bioelectronics for skin cancer management.Biomaterials · 2026Review
- Durable complete response in a patient with BRAF-mutated advanced melanoma with ocular and skin toxicities from BRAF/MEK targeted therapy after checkpoint inhibitor treatment: a case report.Dermatology reports · 2026Article
- Molecular convergence enables precision medicine for pediatric low grade gliomas.Discover oncology · 2026Review
- The dynamics of mutational selection in cutaneous squamous carcinogenesis.Communications biology · 2026Article
- SOX2 confers tumour permissiveness in a specific skin progenitor population.Nature communications · 2026Article
- BRAF V600E-mutated metastatic Wilms tumor with complete response to targeted RAF/MEK inhibition: a post-treatment follow-up case report.Frontiers in oncology · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Advances in Targeted and Immunotherapy for High-Risk Cutaneous Malignancies.Oncology research · 2026Review
- Advanced Cutaneous Squamous Cell Carcinoma: Biology, Immunotherapy, and Evolving Prognostic Factors.Biomedicines · 2025Review
396 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
53 authors at 14 institutions in 6 countries.
Funding
Abstract
backgroundCutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors.
methodsWe performed a molecular analysis to identify oncogenic mutations (HRAS, KRAS, NRAS, CDKN2A, and TP53) in the lesions from patients treated with the BRAF inhibitor vemurafenib. An analysis of an independent validation set and functional studies with BRAF inhibitors in the presence of the prevalent RAS mutation was also performed.
resultsAmong 21 tumor samples, 13 had RAS mutations (12 in HRAS). In a validation set of 14 samples, 8 had RAS mutations (4 in HRAS). Thus, 60% (21 of 35) of the specimens harbored RAS mutations, the most prevalent being HRAS Q61L. Increased proliferation of HRAS Q61L-mutant cell lines exposed to vemurafenib was associated with mitogen-activated protein kinase (MAPK)-pathway signaling and activation of ERK-mediated transcription. In a mouse model of HRAS Q61L-mediated skin carcinogenesis, the vemurafenib analogue PLX4720 was not an initiator or a promoter of carcinogenesis but accelerated growth of the lesions harboring HRAS mutations, and this growth was blocked by concomitant treatment with a MEK inhibitor.
conclusionsMutations in RAS, particularly HRAS, are frequent in cutaneous squamous-cell carcinomas and keratoacanthomas that develop in patients treated with vemurafenib. The molecular mechanism is consistent with the paradoxical activation of MAPK signaling and leads to accelerated growth of these lesions. (Funded by Hoffmann-La Roche and others; ClinicalTrials.gov numbers, NCT00405587, NCT00949702, NCT01001299, and NCT01006980.).
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.