Targeting the epigenome—the regulators that turn on and off the activity of genes—has long been viewed as a promising way to treat cancer. But despite the promise of this approach, early efforts brought few successes in part because of the broad effects of hitting these targets. Constellation Pharmaceuticals is taking a next-generation approach to epigenetics, targeting what it calls the writer, reader, and eraser classes of epigenetic regulators to modulate gene expression in a highly selective manner. It believes its approach can be used to both induce cancer cell killing, as well as enhance anti-tumor immunity. We spoke to Jigar Raythatha, president and CEO of Constellation Pharmaceuticals, about epigenetics, the company’s approach to developing highly selective therapies that target gene regulators, and its programs in myelofibrosis and prostate cancer.