Targeting EGFR in Triple Negative Breast Cancer

Abstract

Our preliminary data show that erlotinib inhibits Triple-negative breast cancer (TNBC) in a xenograft model. However, inhibition of metastasis by erlotinib is accompanied by nonspecific effects because erlotinib can inhibit other kinases; thus, more direct targets that regulate TNBC metastasis need to be identified to improve its therapeutic efficacy.

Keywords: EGFR; erlotinib; metastasis; triple negative breast cancer; tyrosine kinase inhibitor.

Fig 1

EGFR inhibitor induced a change from mesenchymal to epithelial phenotype in TNBC cells. A,SUM149 TNBC cells were grown (3D culture) in the presence of 0 or 0.1 μM erlotinib, an EGFR tyrosine kinase inhibitor. Erlotinib (0.1 μM) inhibited the formation of projections in 3D models at 24 h. In 2D culture, no projections formed. B,Immunostaining performed after 24 h of treatment with erlotinib shows upregulation of epithelial marker E-cadherin, cell membrane localization of β-catenin, and inhibition of mesenchymal marker vimentin. The figure is referenced from Clin Cancer Res. 2009;15(21):6639-48.

Fig 2

Erlotinib inhibited tumor growth and metastasis in a SUM149 xenograft model. A, Tumor volumes in 4 groups of mice (vehicle, 25, 50, and 100 mg/kg erlotinib) were measured weekly. Each data point represents the mean tumor volume of 7 mice per group; bars, SD. B, Findings on ex vivo imaging of lung tissues to detect metastatic tumors in a control (vehicle) mouse and a 25-mg/kg erlotinib-treated mouse. C, Hematoxylin and eosin staining of a lung tissue section from a control mouse at the endpoint of the study showed 2 small deposits of metastatic tumors (arrowheads) in the alveolar septae. D, The incidence of lung metastasis in the 4 groups of mice. E, Immunohistochemical analysis of p-EGFR, p-ERK, E-cadherin, and vimentin in tumor tissues of SUM149 xenografts. The figure is referenced from Clin Cancer Res. 2009;15(21):6639-48.