Epigenetic Therapies in Solid Tumours: From Preclinical Models to Clinical Trial Results

Combining DNA methyltransferase and histone deacetylase inhibition to treat acute myeloid leukemia/myelodysplastic syndrome: Achievements and challenges

“…Already in 1982, shortly after the discovery of 5‐azacytidine (5‐aza) and 5‐aza‐2′‐deoxycytidine (decitabine [DAC]) as powerful DNA‐hypomethylating agents, Jahangeer and colleagues reported that treatment of HeLa cells with 5‐aza followed by butyrate, a histone deacetylase (HDAC) inhibitor, induced β‐adrenergic receptor expression in a synergistic fashion . This probably first report of combination treatment with 2 chromatin‐modifying agents, was followed by many other in vitro studies combining the DNA methyltransferase (Dnmt) inhibitors 5‐aza and DAC with different HDAC inhibitors to enhance their antineoplastic potency . For instance, as reported in a landmark article by Cameron et al, who applied sequential treatment with DAC and trichostatin A, several cell cycle‐associated genes that are epigenetically silenced in colorectal cancer and acute myeloid leukemia (AML) cells were induced synergistically by this combination, providing a rationale for clinical trials using this approach.…”