ArticleCancer discovery2015
EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma.
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 72 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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Who cites it
72 citing papers in PubMed, 122 citations in OpenAlex.
- Understanding and overcoming innate and acquired MAPK inhibition resistance in anaplastic thyroid cancer.Cell reports. Medicine · 2026Article
- Article
- Development of aCellular oncology (Dordrecht, Netherlands) · 2025Article
- The PLEKHA1-TACC2 fusion gene drives tumorigenesis via vascular mimicry formation in esophageal squamous-cell carcinoma.Cell death and differentiation · 2025Article
- 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
- Eph/ephrin-mediated immune modulation: a potential therapeutic target.Frontiers in immunology · 2025Review
- The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.Cells · 2024Article
- Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.Journal of molecular medicine (Berlin, Germany) · 2024Review
- CircRTTN upregulates EPHA2 to aggravate the malignant process of melanoma via sponging miR-890.Histology and histopathology · 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
- Receptor tyrosine kinase inhibitors in cancer.Cellular and molecular life sciences : CMLS · 2023Review
- Ligand-independent EphA2 contributes to chemoresistance in small-cell lung cancer by enhancing PRMT1-mediated SOX2 methylation.Cancer science · 2023Article
- Integrated molecular and clinical analysis of BRAF-mutant glioma in adults.NPJ precision oncology · 2023Article
- ABL1/2 and DDR1 Drive MEKi Resistance in NRAS-Mutant Melanomas by Stabilizing RAF/MYC/ETS1 and Promoting RAF Homodimerization.Cancers · 2023Article
- Eph Receptors in Cancer.Biomedicines · 2023Review
- Development of an In-House EphA2 ELISA for Human Serum and Measurement of Circulating Levels of EphA2 in Hypertensive Patients with Renal Dysfunction.Diagnostics (Basel, Switzerland) · 2022Article
- Exosomes and their roles in the chemoresistance of pancreatic cancer.Cancer medicine · 2022Review
- Targefrin: A Potent Agent Targeting the Ligand Binding Domain of EphA2.Journal of medicinal chemistry · 2022Article
12 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
12 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledBRAF(V600E) is the most common oncogenic lesion in melanoma and results in constitutive activation of the MAPK pathway and uncontrolled cell growth. Selective BRAF inhibitors such as vemurafenib have been shown to neutralize oncogenic signaling, restrain cellular growth, and improve patient outcome. Although several mechanisms of vemurafenib resistance have been described, directed solutions to overcome these resistance lesions are still lacking. Herein, we found that vemurafenib resistance can be (i) mediated by EPHA2, a member of the largest receptor tyrosine kinases (RTK) subfamily erythropoietin-producing hepatocellular (EPH) receptors, and (ii) associated with a greater phenotypic dependence on EPHA2. Furthermore, we developed a series of first-in-class EPHA2 inhibitors and show that these new compounds potently induce apoptosis, suppress viability, and abrogate tumorigenic growth of melanoma cells, including those that are resistant to vemurafenib. These results provide proof of concept that RTK-guided growth, and therapeutic resistance, can be prospectively defined and selectively targeted. SIGNIFICANCE: In this study, we show that resistance to selective BRAF inhibitors can be mediated by the RTK EPHA2. Furthermore, direct targeting of EPHA2 can successfully suppress melanoma growth and mitigate therapeutic resistance.
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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.