ArticleNeoplasia (New York, N.Y.)2010
Pharmacodynamic characterization of the efficacy signals due to selective BRAF inhibition with PLX4032 in malignant melanoma.
Article in Neoplasia (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Guidelines for biomarker testing in metastatic melanoma: a National Consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2014Guideline
- Trial
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- Melanocortin 1 receptor mediates melanin production by interacting with the BBSome in primary cilia.PLoS biology · 2024Article
- Dermaseptin B2 bioactive gene's potential for anticancer and anti-proliferative effect is linked to the regulation of the BAX/BBC3/AKT pathway.Medical oncology (Northwood, London, England) · 2024Article
- WNT5A-ROR2 axis mediates VEGF dependence of BRAF mutant melanoma.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Bilirubin Restrains the Anticancer Effect of Vemurafenib on BRAF-Mutant Melanoma Cells Through ERK-MNK1 Signaling.Frontiers in oncology · 2021Article
- Diverse Mechanisms of BRAF Inhibitor Resistance in Melanoma Identified in Clinical and Preclinical Studies.Frontiers in oncology · 2019Review
- A Convergence-Based Framework for Cancer Drug Resistance.Cancer cell · 2018Review
- Receptor tyrosine kinases and downstream pathways as druggable targets for cancer treatment: the current arsenal of inhibitors.Molecular cancer · 2018Review
- The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function.Cancer discovery · 2017Article
- Vemurafenib and trametinib reduce expression of CTGF and IL-8 inLaboratory investigation; a journal of technical methods and pathology · 2017Article
- Fibroblast-induced switching to the mesenchymal-like phenotype and PI3K/mTOR signaling protects melanoma cells from BRAF inhibitors.Oncotarget · 2016Article
- Optimising the combination dosing strategy of abemaciclib and vemurafenib in BRAF-mutated melanoma xenograft tumours.British journal of cancer · 2016Article
- The Wnts of change: How Wnts regulate phenotype switching in melanoma.Biochimica et biophysica acta · 2015Review
- Review
- Microphthalmia-associated transcription factor in melanoma development and MAP-kinase pathway targeted therapy.Pigment cell & melanoma research · 2015Review
- In silico identification of novel kinase inhibitors by targeting B-Raf(v660e) from natural products database.Journal of molecular modeling · 2015Article
- Molecular and immunohistochemical characterization reveals novel BRAF mutations in metanephric adenoma.The American journal of surgical pathology · 2015Article
- Phosphoproteomic Analysis of Cell-Based Resistance to BRAF Inhibitor Therapy in Melanoma.Frontiers in oncology · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAbout 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma viral oncogene homolog B1 (BRAF) that causes the steady-state activation of extracellular signal-regulated kinase (ERK). We sought to investigate the efficacy of PLX4032 (BRAF inhibitor) to identify patterns/predictors of response/resistance and to study the effects of BRAF in melanoma. EXPERIMENTAL
designWell-characterized melanoma cell lines, including several with acquired drug resistance, were exposed to PLX4032. Growth inhibition, phosphosignaling, cell cycle, apoptosis, and gene expression analyses were performed before and after exposure to drug.
resultsUsing a growth-adjusted inhibitory concentration of 50% cutoff of 1 microM, 13 of 35 cell lines were sensitive to PLX4032, 16 resistant, and 6 intermediate (37%, 46%, and 17% respectively). PLX4032 caused growth inhibition, G(0)/G(1) arrest, and restored apoptosis in the sensitive cell lines. A BRAF mutation predicted for but did not guarantee a response, whereas a neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF conferred resistance. Cells with concurrent BRAF mutations and melanocortin 1 receptor germ line variants and/or a more differentiated melanocyte genotype had a preferential response. Acquired PLX4032 resistance reestablishes ERK signaling, promotes a nonmelanocytic genotype, and is associated with an increase in the gene expression of certain metallothioneins and mediators of angiogenesis.
conclusionsPLX4032 has robust activity in BRAF mutated melanoma. The preclinical use of this molecule identifies criteria for its proper clinical application, describes patterns of and reasons for response/resistance, and affords insight into the role of a BRAF mutation in melanoma.
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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.