Cancer

Cell culture studies suggest inhibiting NEK9 or MAP2K4 could help treat PI3K inhibitor-resistant triple-negative breast cancer (TNBC). In tumor samples from patient-derived xenograft (PDX) mouse models of TNBC, levels of NEK9 and MAP2K4 were higher in tumors resistant to the PI3K inhibitor buparlisib than in buparlisib-sensitive tumors. In two human buparlisib-resistant TNBC cell lines, buparlisib plus shRNA targeting NEK9 or MAP2K4 decreased proliferation compared with buparlisib alone. In tumor cells from one of the buparlisib-resistant PDX mouse models of TNBC, buparlisib plus shRNA targeting NEK9 or MAP2K4 decreased colony formation compared with any agent alone. Next steps could include identifying and testing NEK9 or MAP2K4 inhibitors in models of PI3K inhibitor-resistant TNBC...