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Updated: Apr 23, 2026

Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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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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Integrin-mediated resistance to epidermal growth factor receptor-targeted therapy: an inflammatory situation

Wells S Brown, Michael K Wendt

    Breast Cancer Research : BCR
    |September 27, 2014
    PubMed

    Insights

    Unligated αvβ3 integrin promotes stem-like properties in breast cancer, causing resistance to epidermal growth factor receptor (EGFR) therapies. This pathway involves KRAS:RalB:NF-κB, offering new targets for treatment.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cell Biology

    Background:

    • Targeting epidermal growth factor receptor (EGFR) is ineffective for breast cancer due to inherent resistance.
    • Epithelial-mesenchymal transition (EMT) can lead to stem-like properties, contributing to therapeutic resistance.
    • Understanding resistance mechanisms is crucial for developing effective breast cancer treatments.

    Purpose of the Study:

    • To investigate the role of unligated αvβ3 integrin in mediating stem-like phenotypes in breast cancer.
    • To elucidate the downstream signaling pathway involved in αvβ3 integrin-mediated resistance.
    • To identify potential strategies for overcoming resistance to EGFR-targeted therapies.

    Main Methods:

    • The study utilized cell culture models of breast cancer.
    • Functional assays were performed to assess stem-like properties and drug resistance.
    • Western blotting and pathway analysis were employed to investigate downstream signaling.

    Main Results:

    • Unligated αvβ3 integrin was found to be functionally important in conferring a stem-like phenotype.
    • This integrin mediated resistance to EGFR-targeted therapy.
    • A KRAS:RalB:NF-κB pathway was identified as a key downstream mediator.

    Conclusions:

    • Unligated αvβ3 integrin plays a critical role in breast cancer stemness and resistance to EGFR inhibitors.
    • The KRAS:RalB:NF-κB pathway is a crucial mediator of this resistance mechanism.
    • Targeting this pathway may represent a novel strategy to sensitize breast cancer to EGFR-targeted therapies.

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