SPRED2 and breast cancer: Similarly, downregulation of Sprouty-related EVH1 domain containing 2 (SPRED2), a member of the Sprouty family of RAS inhibitors, frequently altered in breast cancer due to deletion or promoter methylation, leads to tamoxifen resistance, which can be overcome in breast cancer cell lines by a combination of the ERK 1/2 inhibitor ulixertinib with tamoxifen [112].