Michael Haffner, MD, PhD

All cells in the human body have the same DNA, but different types of cells do different jobs. This happens because cells follow extra instructions that tell them how to behave. These instructions are part of a system called epigenetics. One important epigenetic marker is called DNA methylation. It is a small chemical tag on DNA that helps cells work the right way.In many aggressive cancers, large parts of the DNA lose these chemical tags. When this happens, the cancer often grows faster and is harder to treat. Until now, we have not known how to use this information to help choose better treatments.We found that cancers with low DNA methylation have a weakness. Their cells depend strongly on a growth signal called AKT to survive. Drugs that block AKT can slow down or kill these cancer cells. When AKT is blocked, the cancer cells become even more dependent on another system called PRC2, which helps control which genes are turned on or off. By blocking both AKT and PRC2 at the same time, we were able to kill cancer cells much more effectively.Based on these results, we believe low DNA methylation can be used to provide a clue that helps choose the best treatment. We plan to test drug combinations in a clinical study and develop simple tests to see how well the treatment works. If successful, this approach could lead to a more personalized treatment for patients with cancer.