Epigenetic Therapies Move Into New Territory, but How Exactly Do They Work?

Extract

Although several drugs aimed at reversing epigenetic modifications—nonsequence changes in DNA—are already the standard of care for some malignancies, the field scaled a major hurdle this spring when investigators showed for the first time that an epigenetic therapy improved overall survival in a randomized phase III trial.

An international team, known as the International Vidaza High-Risk MDS Survival Study Group, showed that patients with myelodysplastic syndrome who received azacytidine (Vidaza) survived longer than patients who received other standard treatments.

Those data move epigenetics and agents that target epigenetic modifications onto more secure footing in the cancer research community. But even as new therapies are in development, major questions remain with respect to exactly how the agents are working.

“I think the mechanism of action in cell culture models is pretty good, and in xenograft models,” said Peter A. Jones, Ph.D. , director of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, who is credited with the discovery of azacytidine. “So the question is whether or not the same mechanism of action applies in humans—and the answer is still clearly we don’t know.”