Emerging epigenetic therapeutics for myeloid leukemia: modulating demethylase activity with ascorbate.

Emerging epigenetic therapeutics for myeloid leukemia: modulating demethylase activity with ascorbate. Haematologica. 2020 Oct 22;Online ahead of print: Authors: Das AB, Smith-Díaz CC, Vissers MCM Abstract The past decade has seen a proliferation of drugs that target epigenetic pathways. Many of these drugs were developed to treat acute myeloid leukemia, a condition in which dysregulation of the epigenetic landscape is well established. While these drugs have shown promise, critical issues persist. Specifically, patients with the same mutations respond quite differently to treatment. This is true even with highly specific drugs that are designed to target the underlying oncogenic driver mutations. Furthermore, patients who do respond may eventually develop resistance. There is now evidence that epigenetic heterogeneity contributes, in part, to these issues. Cancer cells also have a remarkable capacity to 'rewire' themselves at the epigenetic level in response to drug treatment, and thereby maintain expression of key oncogenes. This epigenetic plasticity is a promising new target for drug development. It is therefore important to consider combination therapy in cases in which both driver mutations and epigenetic plasticity are targeted. Using ascorbate as an example of an emerging epigenetic therapeutic, we review the evidence for its potential use in both of these modes. We provide an overview of 2-oxoglutarate dependent dioxygenase...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research