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Updated: Apr 23, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
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Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

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Epigenetic changes of EGFR have an important role in BRAF inhibitor-resistant cutaneous melanomas

Jinhua Wang1, Sharon K Huang1, Diego M Marzese1

  • 1Department of Molecular Oncology, John Wayne Cancer Institute, Santa Monica, California, USA.

The Journal of Investigative Dermatology
|September 23, 2014
PubMed

Insights

Drug resistance in melanoma is a challenge. This study reveals that epigenetic activation of EGFR drives resistance to BRAF inhibitors by enhancing cell metastasis and activating key signaling pathways, suggesting EGFR inhibitors as a potential treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • BRAF mutations are common in cutaneous melanoma, and BRAF inhibitors (BRAFi) offer significant clinical benefits.
  • Acquired resistance to BRAFi is a major clinical challenge, leading to tumor progression.
  • The precise mechanisms underlying BRAFi resistance in melanoma are still debated.

Purpose of the Study:

  • To investigate the mechanisms of acquired resistance to BRAF inhibitors in melanoma.
  • To identify potential therapeutic targets for overcoming BRAFi resistance.

Main Methods:

  • Development of BRAFi-resistant melanoma cell lines.
  • Analysis of epithelial to mesenchymal transition (EMT) properties.
  • Assessment of Epidermal Growth Factor Receptor (EGFR) expression and its regulatory elements.
  • Investigation of the PI3K/AKT signaling pathway.
  • Evaluation of EGFR inhibitor efficacy in resistant cells.

Main Results:

  • BRAFi-resistant melanoma cells exhibited enhanced metastatic properties (EMT).
  • EGFR was upregulated in resistant cells and patient tumors due to demethylation of regulatory DNA.
  • EGFR activation led to PI3K/AKT pathway activation via epigenetic mechanisms.
  • EGFR inhibition demonstrated effectiveness against BRAFi-resistant melanoma cells.

Conclusions:

  • Epigenetic activation of EGFR plays a critical role in mediating BRAFi resistance in melanoma.
  • Targeting EGFR offers a promising therapeutic strategy for patients with BRAFi-resistant melanoma.

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