ArticleJournal of the American College of Surgeons2026
Targeting Melanoma-Associated Fibroblasts to Overcome Cancer Stem Cell-Driven Drug Resistance.
Article in Journal of the American College of Surgeons, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcquired resistance to BRAF V600E inhibitors remains a major obstacle in melanoma treatment. We hypothesized that melanoma-initiating cells (MICs), regulated by cancer-associated fibroblasts in the tumor microenvironment, mediate drug resistance through stromal Notch1 signaling. STUDY
designPatient-derived melanoma-associated fibroblasts (MAFs) were engineered to activate Notch1 signaling (MAF N1IC-GFP ) via lentiviral transduction. Drug resistance was assessed using BRAF inhibitor-resistant melanoma cells (451LuBR) in 3-dimensional spheroid co-culture assays with PLX4720 treatment. In vivo efficacy was evaluated in NOD scid gamma mice cografted with 451LuBR cells and MAF N1IC-GFP or control MAF GFP (n = 8/group). Primary endpoints included tumor growth, angiogenesis, and CD271⁺ MIC populations assessed by immunofluorescence and quantitative imaging.
resultsIn vitro, MAF N1IC-GFP suppressed drug-resistant melanoma spheroid formation across PLX4720 concentrations (1 to 100 μM, p < 0.01). In vivo, MAF N1IC-GFP cografting reduced tumor growth by 50% (mean tumor weight, p < 0.01) and bioluminescence signal (p < 0.05). Mechanistically, MAF N1IC-GFP selectively depleted CD271⁺ MICs (~50% reduction in fluorescence intensity, p < 0.01), decreased their proliferation (p < 0.01), and induced apoptosis (p < 0.01).
conclusionsActivating Notch1 signaling in MAFs overcomes BRAF inhibitor resistance by disrupting cancer stem cell niches. This stromal-targeted approach represents a novel therapeutic strategy to complement surgical and systemic therapies in melanoma patients with drug-resistant disease.
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.