ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
BRAF Inhibition Stimulates Melanoma-Associated Macrophages to Drive Tumor Growth.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 127 citations in OpenAlex.
- ESMO-ESTRO consensus statements on the safety of combining radiotherapy with EGFR, ALK, or BRAF/MEK inhibitors.ESMO open · 2026Pooled it
- Targeted therapy in BRAF‑mutant melanoma: Advances and challenges (Review).International journal of oncology · 2026Review
- BRAF Inhibition-Associated Nuclear Remodeling is Linked to Cancer-Associated Fibroblast Activation.Cancer research communications · 2026Article
- Genomic, Clinical, and Spatial Predictors of Durable Response to BRAF/MEK Inhibition inbioRxiv : the preprint server for biology · 2026Article
- Systemic treatment for a young patient with stage IV melanoma: A case report.Oncology letters · 2026Article
- Advances in Targeted and Immunotherapy for High-Risk Cutaneous Malignancies.Oncology research · 2026Review
- BRAF mutation and tumor immune microenvironment in new era.American journal of cancer research · 2026Review
- Tumor Microenvironment-Responsive Nanomedicine: Monitoring and Modulating the Tumor Microenvironment for Precision Cancer Therapy.International journal of nanomedicine · 2026Review
- Dual roles and therapeutic targeting of tumor-associated macrophages in tumor microenvironments.Signal transduction and targeted therapy · 2025Review
- Immunomodulation on tumor immune microenvironment in acquired targeted therapy resistance and implication for immunotherapy resistance.Translational oncology · 2025Review
- Navigating Therapeutic Challenges in BRAF-Mutated NSCLC: Non-V600 Mutations, Immunotherapy, and Overcoming Resistance.International journal of molecular sciences · 2024Review
- Patient-Derived Melanoma Immune-Tumoroids as a Platform for Precise High throughput Drug Screening.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Inflammatory signaling in targeted therapy resistance: focus on EGFR-targeted treatment.Cancer biology & medicine · 2024Article
- Off-targets of BRAF inhibitors disrupt endothelial signaling and vascular barrier function.Life science alliance · 2024Article
- Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance.Cell reports. Medicine · 2024Article
- Review
- Article
- Tattoo-Associated Skin Reaction in a Melanoma Patient Receiving B-RAF and MEK Inhibitors: A Case Report with an Emphasis on Etiopathogenic and Histological Features.Journal of clinical medicine · 2024Article
- Revisiting the Role of B-RAF Kinase as a Therapeutic Target in Melanoma.Current medicinal chemistry · 2024Article
- Regulation of ferroptosis-related genes in CD8+ NKT cells and classical monocytes may affect the immunotherapy response after combined treatment in triple negative breast cancer.Thoracic cancer · 2023Article
24 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
22 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo investigate the roles of melanoma-associated macrophages in melanoma resistance to BRAF inhibitors (BRAFi). EXPERIMENTAL
designAn in vitro macrophage and melanoma cell coculture system was used to investigate whether macrophages play a role in melanoma resistance to BRAFi. The effects of macrophages in tumor resistance were examined by proliferation assay, cell death assay, and Western blot analyses. Furthermore, two mouse preclinical models were used to validate whether targeting macrophages can increase the antitumor activity of BRAFi. Finally, the number of macrophages in melanoma tissues was examined by immunohistochemistry.
resultsWe demonstrate that in BRAF-mutant melanomas, BRAFi paradoxically activate the mitogen-activated protein kinase (MAPK) pathway in macrophages to produce VEGF, which reactivates the MAPK pathway and stimulates cell growth in melanoma cells. Blocking the MAPK pathway or VEGF signaling then reverses macrophage-mediated resistance. Targeting macrophages increases the antitumor activity of BRAFi in mouse and human tumor models. The presence of macrophages in melanomas predicts early relapse after therapy.
conclusionsOur findings demonstrate that macrophages play a critical role in melanoma resistance to BRAFi, suggesting that targeting macrophages will benefit patients with BRAF-mutant melanoma.
Indexed as
Identifiers
What OpenQuestion holds
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.