MEK5-ERK5 pathway associates with poor survival of breast cancer patients after systemic treatments

Abstract

The MEK5-ERK5 pathway is a mammalian mitogen-activated protein (MAP) kinase cascade that is not well studied compared to other MAP kinase cascades. Two independent studies by Al-Ejeh et al. and Ortiz-Ruiz et al. published in Oncotarget last year concluded that ERK5 is an attractive target in triple negative breast cancer. In this perspective, we briefly describe the findings of these studies and propose the use of pharmacological inhibition of ERK5 in combination with chemotherapy against triple negative breast cancer because MEK5-ERK5 overexpression associates with poor survival of patients treated with chemotherapy.

Keywords: ERK5/MAPK7; MEK5/MAP2K5; TNBC; chemo-resistance; triple negative breast cancer.

Figure 1. MEK5-ERK5 mRNA expression associates with poor survival after systemic treatments

(A) Relapse-free survival (top row) and distant metastasis-free survival (middle row) of basal-like breast cancer were analyzed in subsets of patients who did not receive or received chemotherapy (No chemotherapy vs. Chemotherapy). (B) Distant metastasis-free survival of HER2-enriched breast cancer in subsets of patients who did not receive systemic treatments or received systemic treatments (No sys. treatment vs. Sys. treatment). The KM Plotter Online Tool was used to carry out the analyses. Patients were stratified according to the average expression level of MEK5 and ERK5. The number of patients in the lower tertile (low; bottom 33%), the upper tertile (high, top 33%) and the middle tertile (intermediate; interm) groups are indicated in parentheses. HR and log-rank p-value (p) for each analysis were obtained using GraphPad^® Prism by comparing the survival of patients in the upper tertile (High) to those in the lower tertile (Low).