A One-Two Epigenetic Punch Against Aggressive Acute Myeloid Leukemia

Scientists have developed a system that uses cancer patients’ own cells to evaluate the efficacy of treatments. The scientists used their new test bed to show that a two-drug combination potentially would benefit many patients with acute myeloid leukemia (AML).

The treatments tested are known as epigenetic drugs. Epigenetic regulation refers to the programming of the genome to switch some genes on and keeps others off within cells. AML features major epigenetic disruptions, and some of the newer cancer drugs are designed to reverse or ameliorate such disruptions. In the study, published online May 10 in Cancer Discovery, the scientists found that the combination of two treatments with distinct epigenetic effects, the U.S. Food and Drug Administration-approved azacytidine and drugs targeting an epigenetic protein called LSD1 currently in clinical trials, was more effective than either drug alone against AML cells from patients—especially so in cells from patients with a chemotherapy resistant type of AML.

This successful test, which is being followed by clinical trials of the drug combination, was made possible because the scientists were able to develop a new system or “platform” for testing epigenetic treatments. The platform allows researchers to keep patients’ cancerous cells alive long enough to study their genetic and epigenetic disruptions and to analyze the molecular details of how they respond to drug treatments.


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