Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2013
Phase II trial of MEK inhibitor selumetinib (AZD6244, ARRY-142886) in patients with BRAFV600E/K-mutated melanoma.
Trial report 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. Cited by 78 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 138 citations in OpenAlex.
- Population Pharmacokinetics of Selumetinib and Its Metabolite N-desmethyl-selumetinib in Adult Patients With Advanced Solid Tumors and Children With Low-Grade Gliomas.CPT: pharmacometrics & systems pharmacology · 2017Trial
- A Retrospective Evaluation of Vemurafenib as Treatment for BRAF-Mutant Melanoma Brain Metastases.The oncologist · 2015Trial
- Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Review
- Dissecting the MAPK signaling landscape in malignant melanoma: from BRAF and NRAS mutations to precision combination therapies.Frontiers in cell and developmental biology · 2025Review
- Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- The anti-cancer effect and mechanism of animal scale-derived extract on malignant melanoma cells.Scientific reports · 2023Article
- Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results From Two Phase I Trials.The oncologist · 2023Article
- Targeting RAS-RAF-MEK-ERK signaling pathway in human cancer: Current status in clinical trials.Genes & diseases · 2023Review
- Radio-sensitizing effect of MEK inhibition in glioblastoma in vitro and in vivo.Journal of cancer research and clinical oncology · 2023Article
- Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy.Molecular biomedicine · 2022Review
- DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition.Cancer discovery · 2022Article
- Phase I study of cediranib, an oral VEGFR inhibitor, in combination with selumetinib, an oral MEK inhibitor, in patients with advanced solid malignancies.Investigational new drugs · 2022Article
- Polyglutamate-based nanoconjugates for image-guided surgery and post-operative melanoma metastases prevention.Theranostics · 2022Article
- Clinical Pharmacokinetics and Pharmacodynamics of Selumetinib.Clinical pharmacokinetics · 2021Review
- Advanced Melanoma: Resistance Mechanisms to Current Therapies.Hematology/oncology clinics of North America · 2021Review
- Genomic and pathological heterogeneity in clinically diagnosed small cell lung cancer in never/light smokers identifies therapeutically targetable alterations.Molecular oncology · 2021Article
- Mechanisms of Resistance to BRAF-Targeted Melanoma Therapies.American journal of clinical dermatology · 2021Article
- Cellular Plasticity in Breast Cancer Progression and Therapy.Frontiers in molecular biosciences · 2020Review
18 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
13 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTest the hypothesis that in BRAF-mutated melanomas, clinical responses to selumetinib, a MEK inhibitor, will be restricted to tumors in which the PI3K/AKT pathway is not activated. EXPERIMENTAL
designWe conducted a phase II trial in patients with melanoma whose tumors harbored a BRAF mutation. Patients were stratified by phosphorylated-AKT (pAKT) expression (high vs. low) and treated with selumetinib 75 mg per os twice daily. Pretreatment tumors were also analyzed for genetic changes in 230 genes of interest using an exon-capture approach.
resultsThe high pAKT cohort was closed after no responses were seen in the first 10 patients. The incidence of low pAKT melanoma tumors was low (∼25% of melanomas tested) and this cohort was eventually closed because of poor accrual. However, among the five patients with melanoma accrued in the low pAKT cohort, there was one partial response (PR). Two other patients had near PRs before undergoing surgical resection of residual disease (one patient) or discontinuation of treatment due to toxicity (one patient). Among the two nonresponding, low pAKT patients with melanoma, co-mutations in MAP2K1, NF1, and/or EGFR were detected.
conclusionsTumor regression was seen in three of five patients with BRAF-mutated, low pAKT melanomas; no responses were seen in the high pAKT cohort. These results provide rationale for co-targeting MEK and PI3K/AKT in patients with BRAF mutant melanoma whose tumors express high pAKT. However, the complexity of genetic changes in melanoma indicates that additional genetic information will be needed for optimal selection of patients likely to respond to MEK 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.