Trial reportCancer discovery2014
MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition.
Trial report in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 300 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
300 citing papers in PubMed, 1 synthesis or guideline pooled it, 472 citations in OpenAlex.
- Clinical Activity of Mitogen-Activated Protein Kinase Inhibitors in Patients With MAP2K1 (MEK1)-Mutated Metastatic Cancers.JCO precision oncology · 2025Pooled it
- Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial.JAMA oncology · 2017Trial
- Review
- PredictedInternational journal of molecular sciences · 2026Article
- Tissue-Level Transcriptomic Entropy Reveals Organ-Specific Aging Patterns and Predicts Cancer Progression.Aging cell · 2026Article
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Loss of ten-eleven translocation 2 (TET2) facilitates aggressive behaviour in cutaneous melanoma by inducing peroxisome proliferator-activated receptor-γ coactivator 1α expression and oxidative phosphorylation.The British journal of dermatology · 2026Article
- Gene editing in cancer therapy: overcoming drug resistance and enhancing precision medicine.Cancer gene therapy · 2025Review
- Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models.Nature communications · 2025Article
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- GPNMB marks a quiescent cell population in melanoma and promotes metastasis formation.EMBO reports · 2025Article
- Sensitivity to immune checkpoint inhibitors in BRAF/MEK inhibitor refractory melanoma.Journal for immunotherapy of cancer · 2025Article
- BRAF Targeting Across Solid Tumors: Molecular Aspects and Clinical Applications.International journal of molecular sciences · 2025Review
- FAK inhibition combined with the RAF-MEK clamp avutometinib overcomes resistance to targeted and immune therapies in BRAF V600E melanoma.Cancer cell · 2025Article
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Global trends and emerging insights in BRAF and MEK inhibitor resistance in melanoma: a bibliometric analysis.Frontiers in molecular biosciences · 2025Article
- Acquired resistance to molecularly targeted therapies for cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Conjunctival melanoma: comprehensive insights into clinical features, genetic alterations, and modern treatment approaches.Pathology oncology research : POR · 2025Review
- Article
240 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 7 institutions in 1 country.
Funding
Abstract
Treatment of BRAF-mutant melanoma with combined dabrafenib and trametinib, which target RAF and the downstream MAP-ERK kinase (MEK)1 and MEK2 kinases, respectively, improves progression-free survival and response rates compared with dabrafenib monotherapy. Mechanisms of clinical resistance to combined RAF/MEK inhibition are unknown. We performed whole-exome sequencing (WES) and whole-transcriptome sequencing (RNA-seq) on pretreatment and drug-resistant tumors from five patients with acquired resistance to dabrafenib/trametinib. In three of these patients, we identified additional mitogen-activated protein kinase (MAPK) pathway alterations in the resistant tumor that were not detected in the pretreatment tumor, including a novel activating mutation in MEK2 (MEK2(Q60P)). MEK2(Q60P) conferred resistance to combined RAF/MEK inhibition in vitro, but remained sensitive to inhibition of the downstream kinase extracellular signal-regulated kinase (ERK). The continued MAPK signaling-based resistance identified in these patients suggests that alternative dosing of current agents, more potent RAF/MEK inhibitors, and/or inhibition of the downstream kinase ERK may be needed for durable control of BRAF-mutant melanoma.
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.