ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
RAF265 inhibits the growth of advanced human melanoma tumors.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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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.
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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
35 citing papers in PubMed, 62 citations in OpenAlex.
- A first-in-human phase I, multicenter, open-label, dose-escalation study of the oral RAF/VEGFR-2 inhibitor (RAF265) in locally advanced or metastatic melanoma independent from BRAF mutation status.Cancer medicine · 2017Trial
- Article
- RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics.The Journal of clinical investigation · 2021Article
- Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma.Scientific reports · 2021Article
- Membrane Transporters and Channels in Melanoma.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Developments in the Space of New MAPK Pathway Inhibitors for BRAF-Mutant Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Review
- Cell-type dependent enhancer binding of the EWS/ATF1 fusion gene in clear cell sarcomas.Nature communications · 2019Article
- Targeting the ERK Signaling Pathway in Melanoma.International journal of molecular sciences · 2019Review
- Downregulation of RNF128 activates Wnt/β-catenin signaling to induce cellular EMT and stemness via CD44 and CTTN ubiquitination in melanoma.Journal of hematology & oncology · 2019Article
- Safety, tolerability, and pharmacokinetic profile of dabrafenib in Japanese patients with BRAFInvestigational new drugs · 2018Article
- MDM2 Antagonists Counteract Drug-Induced DNA Damage.EBioMedicine · 2017Article
- Searching for the Chokehold of NRAS Mutant Melanoma.The Journal of investigative dermatology · 2016Review
- Connecting the Dots: Therapy-Induced Senescence and a Tumor-Suppressive Immune Microenvironment.Journal of the National Cancer Institute · 2016Article
- Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy.Oncogene · 2016Review
- Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma.Scientific reports · 2016Article
- A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia.Scientific reports · 2016Article
- Biology and treatment of BRAF mutant metastatic melanoma.Melanoma management · 2016Review
- Combined Pan-RAF and MEK Inhibition Overcomes Multiple Resistance Mechanisms to Selective RAF Inhibitors.Molecular cancer therapeutics · 2015Article
- What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment.Oncotarget · 2015Review
- Preclinical analysis of the anti-tumor and anti-metastatic effects of Raf265 on colon cancer cells and CD26(+) cancer stem cells in colorectal carcinoma.Molecular cancer · 2015Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeThe purpose of this preclinical study was to determine the effectiveness of RAF265, a multikinase inhibitor, for treatment of human metastatic melanoma and to characterize traits associated with drug response. EXPERIMENTAL
designAdvanced metastatic melanoma tumors from 34 patients were orthotopically implanted to nude mice. Tumors that grew in mice (17 of 34) were evaluated for response to RAF265 (40 mg/kg, every day) over 30 days. The relation between patient characteristics, gene mutation profile, global gene expression profile, and RAF265 effects on tumor growth, mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation, proliferation, and apoptosis markers was evaluated.
resultsNine of the 17 tumors that successfully implanted (53%) were mutant BRAF (BRAF(V600E/K)), whereas eight of 17 (47%) tumors were BRAF wild type (BRAF(WT)). Tumor implants from 7 of 17 patients (41%) responded to RAF265 treatment with more than 50% reduction in tumor growth. Five of the 7 (71%) responders were BRAF(WT), of which 1 carried c-KIT(L576P) and another N-RAS(Q61R) mutation, while only 2 (29%) of the responding tumors were BRAF(V600E/K). Gene expression microarray data from nonimplanted tumors revealed that responders exhibited enriched expression of genes involved in cell growth, proliferation, development, cell signaling, gene expression, and cancer pathways. Although response to RAF265 did not correlate with pERK1/2 reduction, RAF265 responders did exhibit reduced pMEK1, reduced proliferation based upon reduced Ki-67, cyclin D1 and polo-like kinase1 levels, and induction of the apoptosis mediator BCL2-like 11.
conclusionsOrthotopic implants of patient tumors in mice may predict prognosis and treatment response for melanoma patients. A subpopulation of human melanoma tumors responds to RAF265 and can be characterized by gene mutation and gene expression profiles.
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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.