Perhaps the clearest example to date for which the understanding of mechanism has opened a path for therapeutic development has been in synovial sarcoma (36). Here, the driving, oncogenic mutation is always the same and always results in the addition of exactly 78 amino acids of SSX to the SS18 gene at precisely the same place (88, 90). The fusion protein is incorporated into complexes and then dramatically retargets the BAF complex to oncogenic drivers. Clearly, the cancer-specific SS18-SSX fusion protein is an excellent target for small-molecule therapeutics in much the same way that Bcr-ABL fusions are in chronic myeloid leukemia (122). One would predict that a molecule that would prevent the dominant entry of the SS18-SSX fusion into the BAF complex would prevent tumor growth. This speculation is supported by the fact that overexpressing the wild-type SS18 protein in synovial sarcoma cells leads to reassembly of the normal complex, arrest of cell proliferation, and cell death (36). The precise amino acids that must be targeted are predicted from the sequences of SSX genes that are permissive to tumor development
