While short term dual GDC + SCH therapy effectively reduced phospho-ERK and phospho-FRA1 in UPS tumors, indicative of suppression of the kinase activities of MEK and of ERK, respectively, in the longer term therapeutic studies we identified microscopic nests of tumor cells that displayed no phospho-ERK but abundant phospho-FRA1, suggestive of reactivation or bypass of ERK activity. The gene discussed is MAP2K7; the disease is undifferentiated pleomorphic sarcoma.