title: Integrin-mediated resistance to epidermal growth factor receptor-targeted therapy: an inflammatory situation.
abstract: 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.
authors.forename: Wells S
authors.initials: WS
authors.lastname: Brown
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wendt
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000188:drug therapy*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000378:metabolism*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D039661:Integrin beta3; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D066246:ErbB Receptors; D020725:ral GTP-Binding Proteins; D018631:ras Proteins