In other studies, the presence of a Brg (Smarca4) mutation has been shown to predict sensitivity to a combination of EZH2 and TopoIIa inhibition in a group of small cell lung cancers (120). The underlying mechanism is unclear, but it is possible that EZH2 inhibition blocks Polycomb placement, allowing the binding of TopoIIa to DNA and, hence, sensitivity to these inhibitors in the face of a BAF subunit mutation. However, the speculation that polycomb and its repressive marks block the binding of TopoIIa has not been tested to date.
