In rhabdoid tumors, the definitive mutation is a loss of function of both alleles of BAF47 (SMARCB1, INI1, hSNF5) (61). Because there is no specific fusion to target or gained interaction identified to date, a cancer-specific treatment seems less likely unless the loss of BAF47 produces specific allosteric effects over the complex that would render it uniquely susceptible to small molecules. However, Roberts and colleagues have shown that these cancers have essentially only the initiating BAF47 loss, which suggests that targeting MRT-specific BAF complexes in this setting might be sufficient to initiate tumor regression. The discovery that nearly all of the effects of BAF47 loss could be explained by accumulation of polycomb and its products over the Ink4a locus indicated that polycomb inhibitors may be effective in these cancers. Although not specific for rhabdoid cancers, EZH2 inhibitors could hold hope for this essentially untreatable disease and are already being clinically exploited.
