ArticleCell reports. Medicine2024
Monitoring melanoma patients on treatment reveals a distinct macrophage population driving targeted therapy resistance.
Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Exploratory Analysis of Biomarkers and Treatment Outcomes from the COLUMBUS Study in BRAF V600E/K-Mutant Advanced or Metastatic Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Tebentafusp, a T cell engager, promotes macrophage reprogramming and in combination with IL-2 overcomes macrophage immunosuppression in cancer.Nature communications · 2025Trial
- IGF1-IGF1R signaling in tumor-associated macrophages regulates extracellular matrix organization in BRAF inhibitor-targeted melanoma.Molecular and cellular biochemistry · 2026Article
- Targeting ABL kinases overcomes melanoma immune evasion following resistance to MAPK inhibition.Nature communications · 2026Article
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Spatial transcriptomics reveals influence of microenvironment on intrinsic fates in melanoma therapy resistance.Genome biology · 2026Article
- A Stretchable, Transparent, Photothermally Stimulated Laser-Induced Graphene Patch for Noninvasive Skin Tumor Treatment.ACS nano · 2026Article
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- 5-HT reuptake blockade induces pyroptosis in BRAFCell reports. Medicine · 2026Article
- Machine learning-based development of a cytotoxicity prediction model for NK cell therapy in cancers.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- CST7Translational cancer research · 2025Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to targeted therapy remains a major clinical challenge in melanoma. To uncover resistance mechanisms, we perform single-cell RNA sequencing on fine-needle aspirates from resistant and responding tumors of patients undergoing BRAFi/MEKi treatment. Among the genes most prominently expressed in resistant tumors is POSTN, predicted to signal to a macrophage population associated with targeted therapy resistance (TTR). Accordingly, tumors from patients with fast disease progression after therapy exhibit high POSTN expression levels and high numbers of TTR macrophages. POSTN polarizes human macrophages toward a TTR phenotype and promotes resistance to targeted therapy in a melanoma mouse model, which is associated with a phenotype change in intratumoral macrophages. Finally, polarized TTR macrophages directly protect human melanoma cells from MEKi-induced killing via CD44 receptor expression on melanoma cells. Thus, interfering with the protective activity of TTR macrophages may offer a strategy to overcome resistance to targeted therapy in melanoma.
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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.