Reversing the silencing of tumor suppressor genes is a promising therapeutic strategy. DNA methyltransferase inhibitors (such as azacitidine and decitabine) and histone deacetylase inhibitors (such as vorinostat and romidepsin) are being investigated to reactivate silenced tumor suppressor genes. These agents can demethylate CpG islands and modify histones to restore normal gene expression, thereby re-establishing the tumor-suppressive functions.