ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Tumor genetic analyses of patients with metastatic melanoma treated with the BRAF inhibitor dabrafenib (GSK2118436).
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00880321 (A Phase I, Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the BRAF Inhibitor GSK2118436 in Subjects With Solid Tumors), which is not on this map. Cited by 112 papers, 1 of them a synthesis that pooled it.
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.
A Phase I, Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the BRAF Inhibitor GSK2118436 in Subjects With Solid Tumors
Who cites it
112 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Clinical Activity of Mitogen-Activated Protein Kinase-Targeted Therapies in Patients With Non-V600 BRAF-Mutant Tumors.JCO precision oncology · 2022Pooled it
- Copy Number Changes Are Associated with Response to Treatment with Carboplatin, Paclitaxel, and Sorafenib in Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- A Retrospective Evaluation of Vemurafenib as Treatment for BRAF-Mutant Melanoma Brain Metastases.The oncologist · 2015Trial
- Targeted next generation sequencing identifies clinically actionable mutations in patients with melanoma.Pigment cell & melanoma research · 2014Trial
- Trial
- Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Trial
- Evolving precision: Updates in targeted therapy for cholangiocarcinoma.Hepatology (Baltimore, Md.) · 2026Review
- Macrophages as Drivers of Resistance to Dabrafenib Plus Trametinib Therapy in Anaplastic Thyroid Cancer.International journal of molecular sciences · 2026Article
- Co-targeting CDK4/6 and MEK reverses mesenchymal transition in therapy-refractory BRAF-altered pediatric high-grade glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Understanding the Promise and Challenges of Tumor-Agnostic Therapy: Could One Size Really Fit All?Cancers · 2026Review
- The Roles of PTEN in Melanoma Suppression.Pigment cell & melanoma research · 2025Review
- BRAF Targeting Across Solid Tumors: Molecular Aspects and Clinical Applications.International journal of molecular sciences · 2025Review
- Multiomics Identifies Potential Molecular Profiles Associated With Outcomes After BRAF-Targeted Therapy in Patients With BRAF V600E-Mutated Advanced Solid Tumors.JCO precision oncology · 2025Article
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance.International journal of molecular sciences · 2024Review
- RAF and MEK Inhibitors in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Article
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- BRAF Mutations in Melanoma: Biological Aspects, Therapeutic Implications, and Circulating Biomarkers.Cancers · 2023Review
- BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies.Current treatment options in oncology · 2022Review
52 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
20 authors at 5 institutions in 4 countries.
Funding
Abstract
purposeDabrafenib is a selective inhibitor of V600-mutant BRAF kinase, which recently showed improved progression-free survival (PFS) as compared with dacarbazine, in metastatic melanoma patients. This study examined potential genetic markers associated with response and PFS in the phase I study of dabrafenib. EXPERIMENTAL
designBaseline (pretreatment or archival) melanoma samples were evaluated in 41 patients using a custom genotyping melanoma-specific assay, sequencing of PTEN, and copy number analysis using multiplex ligation amplification and array-based comparative genomic hybridization. Nine patients had on-treatment and/or progression samples available.
resultsAll baseline patient samples had BRAF(V600E/K) confirmed. Baseline PTEN loss/mutation was not associated with best overall response to dabrafenib, but it showed a trend for shorter median PFS [18.3 (95% confidence interval, CI, 9.1-24.3) vs. 32.1 weeks (95% CI, 24.1-33), P=0.059]. Higher copy number of CCND1 (P=0.009) and lower copy number of CDKN2A (P=0.012) at baseline were significantly associated with decreased PFS. Although no melanomas had high-level amplification of BRAF, the two patients with progressive disease as their best response had BRAF copy gain in their tumors.
conclusionsCopy number changes in CDKN2A, CCND1, and mutation/copy number changes in PTEN correlated with the duration of PFS in patients treated with dabrafenib. The results suggest that these markers should be considered in the design and interpretation of future trials with selective BRAF inhibitors in advanced melanoma patients.
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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.