ArticleCancer discovery2015
Ligand-independent EPHA2 signaling drives the adoption of a targeted therapy-mediated metastatic melanoma phenotype.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 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.
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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
70 citing papers in PubMed, 102 citations in OpenAlex.
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Proteolytic EphA2 fragments cooperatively promote hepatocellular carcinoma progression.Cell death & disease · 2026Article
- Antitumor Activities of Chimeric Anti-EphA2 Antibodies in Xenograft Models of Breast, Pancreatic, and Colorectal Cancers.International journal of molecular sciences · 2026Article
- Cetuximab co-treatment with KRAS G12C inhibitors fulzerasib and sotorasib in human KRAS G12C non-small cell lung cancer cells.Cell death discovery · 2026Article
- Targeting EphA2 under DNA damage causes mitotic bypass via p21 induction.The Journal of biological chemistry · 2026Article
- Genetic Insight into Expression-Defined Melanoma Subtypes and Network Mechanisms: An in Silico Study.Genes · 2025Article
- SOX10 Regulates Melanoma Metastasis Through the IRF1-ITGA3/EphA2-FAK Pathway.Cancer science · 2025Article
- Phenotype switching in highly invasive resistant to vemurafenib and cobimetinib melanoma cells.Cell communication and signaling : CCS · 2025Article
- Crosstalk between tumor endothelial cells and cancer cells is important for metastasis initiation.Cell communication and signaling : CCS · 2025Article
- Review
- Lineage dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and -independent immunotherapeutic targets.Neuro-oncology · 2025Article
- EphrinA2 promotes glioma cell migration and invasion through EphA2 and FAK.Cancer cell international · 2025Article
- Phosphatidylinositol 4,5-bisphosphate drives the formation of EGFR and EphA2 complexes.Science advances · 2024Article
- EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.International journal of molecular sciences · 2024Review
- Overview of current melanoma therapies.Pigment cell & melanoma research · 2024Review
- Review
- Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.Journal of molecular medicine (Berlin, Germany) · 2024Review
- SOX10 deficiency-mediated LAMB3 upregulation determines the invasiveness of MAPKi-resistant melanoma.Oncogene · 2024Article
- Cooperative function of oncogenic MAPK signaling and the loss of Pten for melanoma migration through the formation of lamellipodia.Scientific reports · 2024Article
- Eph receptors and ephrins in cancer progression.Nature reviews. Cancer · 2024Review
10 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
20 authors at 6 institutions in 2 countries.
Funding
Abstract
unlabelledMany patients with BRAF inhibitor resistance can develop disease at new sites, suggesting that drug-induced selection pressure drives metastasis. Here, we used mass spectrometry-based phosphoproteomic screening to uncover ligand-independent EPHA2 signaling as an adaptation to BRAF inhibitor therapy that led to the adoption of a metastatic phenotype. The EPHA2-mediated invasion was AKT-dependent and readily reversible upon removal of the drug as well as through PI3K and AKT inhibition. In xenograft models, BRAF inhibition led to the development of EPHA2-positive metastases. A retrospective analysis of patients with melanoma on BRAF inhibitor therapy showed that 68% of those failing therapy develop metastases at new disease sites, compared with 35% of patients on dacarbazine. Further IHC staining of melanoma specimens taken from patients on BRAF inhibitor therapy as well as metastatic samples taken from patients failing therapy showed increased EPHA2 staining. We suggest that inhibition of ligand-independent EPHA2 signaling may limit metastases associated with BRAF inhibitor therapy. SIGNIFICANCE: This study provides evidence that BRAF inhibition promotes the adoption of a reversible, therapy-driven metastatic phenotype in melanoma. The cotargeting of ligand-independent EPHA2 signaling and BRAF may be one strategy to prevent the development of therapy-mediated disease at new sites.
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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.