AXL/epidermal growth factor receptor (EGFR) complexes in breast cancer--culprits for resistance to EGFR inhibitors?

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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure

Published on: August 11, 2017

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Marinus R Heideman, Nancy E Hynes

    Breast Cancer Research : BCR
    |November 1, 2013
    PubMed

    Insights

    Blocking the epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) has shown limited success. New research suggests an interplay between EGFR and the AXL receptor may explain these findings in TNBC treatment.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cancer Research

    Background:

    • Epidermal growth factor receptor (EGFR) is highly expressed in triple-negative breast cancer (TNBC), correlating with poor prognosis.
    • Clinical trials blocking EGFR in TNBC have yielded disappointing results, contrary to oncogene addiction expectations.
    • The underlying reasons for EGFR inhibition failure in TNBC remain largely unexplained.

    Purpose of the Study:

    • To investigate the potential reasons for the lack of clinical efficacy of EGFR blockade in triple-negative breast cancer.
    • To explore the interplay between EGFR and other receptor tyrosine kinases, such as AXL, in TNBC.

    Main Methods:

    • Analysis of EGFR and AXL receptor expression and signaling pathways in TNBC cell lines.
    • Investigating the functional consequences of combined EGFR and AXL receptor blockade.

    Main Results:

    • Meyer and colleagues identified a significant interplay between EGFR and the epithelial-to-mesenchymal transition-associated AXL receptor in TNBC cells.
    • This interaction may contribute to resistance mechanisms against EGFR-targeted therapies in TNBC.

    Conclusions:

    • The interplay between EGFR and AXL receptor signaling represents a potential mechanism for therapeutic resistance in triple-negative breast cancer.
    • Targeting both EGFR and AXL may be a more effective strategy for TNBC treatment.

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