Remarkably, in SS preclinical models, ERK overactivation through diverse mechanisms, such as MKP3 downregulation [107] or NRAS Q61R mutation and deregulated receptor tyrosine kinase activation [68] has been shown to play a relevant role in intrinsic and acquired resistance to the clinically approved drug pazopanib. This evidence concerns the gene DUSP6 and synovial sarcoma.