ArticleJCI insight2018
The RUNX1/IL-34/CSF-1R axis is an autocrinally regulated modulator of resistance to BRAF-V600E inhibition in melanoma.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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.
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Who cites it
25 citing papers in PubMed, 37 citations in OpenAlex.
- Breast Cancer Milieu Maneuvers Cancer-Associated Macrophages to Synergize Neoplastic Repertoires.Cancers · 2026Review
- CSF1R modulates megakaryopoiesis by targeting RUNX1 in immune thrombocytopenia.Haematologica · 2026Article
- Pharmacologic inhibition of CSF-1R suppresses intrinsic tumor cell growth in osteosarcoma with CSF-1R overexpression.Journal of translational medicine · 2025Article
- Tumor associated macrophages as key contributors and targets in current and future therapies for melanoma.Expert review of clinical immunology · 2024Review
- The molecular determinants of microglial developmental dynamics.Nature reviews. Neuroscience · 2024Review
- Role of CSF1R 550th-tryptophan in kusunokinin and CSF1R inhibitor binding and ligand-induced structural effect.Scientific reports · 2024Article
- RUNX transcription factors: biological functions and implications in cancer.Clinical and experimental medicine · 2024Review
- CSF-1R in Cancer: More than a Myeloid Cell Receptor.Cancers · 2024Review
- p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression.Cancer discovery · 2023Article
- Understanding cancer drug resistance withiScience · 2023Article
- Interleukin-34 and immune checkpoint inhibitors: Unified weapons against cancer.Frontiers in oncology · 2023Review
- Recruitment mechanisms and therapeutic implications of tumor-associated macrophages in the glioma microenvironment.Frontiers in immunology · 2023Review
- Macrophage-Colony-Stimulating Factor Receptor Enhances Prostate Cancer Cell Growth and Aggressiveness In Vitro and In Vivo and Increases Osteopontin Expression.International journal of molecular sciences · 2022Article
- Potential Stereoselective Binding ofMolecules (Basel, Switzerland) · 2022Article
- Machine learning approach informs biology of cancer drug response.BMC bioinformatics · 2022Article
- Transcriptional and reverse transcriptional regulation of host genes by human endogenous retroviruses in cancers.Frontiers in microbiology · 2022Review
- BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma.Cancers · 2021Article
- Colony Stimulating Factor 1 Receptor in Acute Myeloid Leukemia.Frontiers in oncology · 2021Review
- Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Interacts With Colony-Stimulating Factor 1 Receptor (CSF1R) but Is Not Necessary for CSF1/CSF1R-Mediated Microglial Survival.Frontiers in immunology · 2021Article
- The twin cytokines interleukin-34 and CSF-1: masterful conductors of macrophage homeostasis.Theranostics · 2021Review
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 1 country.
Funding
Abstract
Resistance to current therapies still impacts a significant number of melanoma patients and can be regulated by epigenetic alterations. Analysis of global cytosine methylation in a cohort of primary melanomas revealed a pattern of early demethylation associated with overexpression of oncogenic transcripts. Loss of methylation and associated overexpression of the CSF 1 receptor (CSF1R) was seen in a majority of tumors and was driven by an alternative, endogenous viral promoter in a subset of samples. CSF1R was particularly elevated in melanomas with BRAF and other MAPK activating mutations. Furthermore, rebound ERK activation after BRAF inhibition was associated with RUNX1-mediated further upregulation of CSF-1R and its ligand IL-34. Importantly, increased CSF-1R and IL-34 overexpression were detected in an independent cohort of resistant melanomas. Inhibition of CSF-1R kinase or decreased CSF-1R expression by RNAi reduced 3-D growth and invasiveness of melanoma cells. Coinhibition of CSF-1R and BRAF resulted in synergistic efficacy in vivo. To our knowledge, our data unveil a previously unknown role for the autocrine-regulated CSF-1R in BRAF V600E resistance and provide a preclinical rationale for targeting this pathway 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.