Integrin-mediated resistance to epidermal growth factor receptor-targeted therapy: an inflammatory situation

Breast Cancer Res. 2014 Sep 23;16(5):448. doi: 10.1186/s13058-014-0448-0.


Targeting the function of epidermal growth factor receptor (EGFR) has failed as an effective clinical option for breast cancer. Understanding the drivers of inherent resistance has been a challenge. One possible mechanism is the acquisition of stem-like properties through the process of epithelial-mesenchymal transition. A recent study by Seguin and colleagues adds to our understanding of this process by demonstrating a functional role for unligated αvβ3 integrin in mediating a stem-like phenotype and facilitating resistance to EGFR-targeted therapy via enhanced downstream coupling to a KRAS:RalB:NF-κB pathway. Importantly, the identified mechanism may reveal a possible strategy for sensitizing breast cancer cells to EGFR-targeted therapies.

Publication types

  • Comment

MeSH terms

  • Animals
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Humans
  • Integrin beta3 / metabolism*
  • Lung Neoplasms / drug therapy*
  • Neoplastic Stem Cells / drug effects*
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins / metabolism*
  • ral GTP-Binding Proteins / metabolism*
  • ras Proteins / metabolism*


  • Integrin beta3
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • ral GTP-Binding Proteins
  • ras Proteins