CHAPTER 9: Who will Benefit from Epigenetic Drugs?

Recently targeted drug discovery effort in oncology has expanded its traditional focus on genetic lesions to epigenetic alterations that directly modulate tumour cell proliferation, survival, migration and differentiation. Both DNA methylation and histone modification regulation has been found dysregulated in cancer. In addition to hypomethylating agents and HDAC inhibitors which have been on the market for several years, additional epigenetic drugs affecting histone methylation and chromatin remodelling have recently entered in clinic. Most of them have been developed for selective patient populations and their indication is being expanded as single agent or combination therapy through a strong effort in translational medicine. Because tumour response to an epigenetic inhibitor may be independent of target expression, mutational status and substrate levels, different approaches may be required to identify responder patients. This chapter will focus on precision medicine approaches applied to epigenetic targets using EZH2, Dot1L and NSD2 as examples.