In this context, we provide proof-of-principle evidence that combined GDC-0623 and SCH772984 therapy is efficacious by showing that short term combination treatment efficiently inhibits MEK and ERK activities in the autochthonous HrasG12V-driven UPS model and that long term therapy inhibits the evolution of macroscopic UPS tumors. Here, MAPK1 is linked to undifferentiated pleomorphic sarcoma.