Inhibition of MEK1/2 by trametinib in patients with triple-negative breast cancer (TNBC) induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTK) comparing tumor samples before and after one week of treatment.
In this study, we analyzed the effects of the MEK1/2 inhibitor selumetinib in combination with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib in a panel of TNBC cell lines that showed different levels of sensitivity to single-agent selumetinib: SUM-149 and MDA-MB-231 cells resulted to be sensitive, whereas SUM-159, MDA-MB-468 and HCC70 cells were relatively resistant to the drug.
To assess the prognostic impact of ERK in TNBC patients, relative quantities of ERK (ERK-2 and pMAPK) and direct targets of the ERK pathway (MAPK/ERK kinase 1, phospho-enriched protein in astrocytes [PEA]-15, phosphorylated (p)PEA-15, tuberous sclerosis protein 2, p70S6 kinase, and p27) were measured using reverse-phase protein arrays in tumor tissue from patients with TNBC (n = 97) and non-TNBC (n = 223).