Depending on SWI/SNF

Gain-of-function alterations in histone-modifying proteins drive multiple cancers and are now being targeted by compounds in the clinic,¹ but loss-of-function mutations, which are more frequently found in chromatin remodelers, remain largely intractable. Separate teams from Japan, Boston and Novartis AG now have identified synthetic lethal interactions that could be exploited to help treat cancers with mutations in the SWI/SNF chromatin-remodeling complex.^2-5

The key question is whether these targets-core regulatory proteins within the SWI/SNF (switch/sucrose nonfermentable) complex-can be selectively inhibited with an acceptable therapeutic index...