New biological targets could lead to therapies for drug-resistant cancers

A study on how Polycombs regulate cellular identity could lead to alternative treatments for patients with drug-resistant cancer.

A team of geneticists from Trinity College Dublin, Ireland has discovered new biological targets that may help devise alternative therapies for cancers that are becoming resistant to existing drugs.

In 2011 scientists discovered that a Polycomb gene, called EZH2, is mutated in lymphomas, a cancer of immune cells and several companies developed drugs to inhibit the activity of EZH2. These targeted treatments are now showing real promise in clinical trials.

However, as with many cancer therapies, resistance has begun to arise, which means scientists will need to develop alternative strategies to fight the cancerous cells. The new discovery provides new clues as to how this might be achieved.

The researchers discovered that EZH2 requires additional “accessory components” to target its activity to key regions in the genome and execute its critical cellular functions. The new results suggest these “accessory components” represent promising alternative targets, which will be needed for oncologists to treat patients who develop resistance to existing EZH2 inhibitor drugs.

“This new discovery was driven purely by our curiosity to understand how Polycombs regulate cellular identity, but we also anticipate that it will lead to new opportunities to develop alternative treatments for patients with cancers driven by mutations in EZH2 and its related genes,” said Professor Adrian Bracken, Associate Professor in Genetics at Trinity College Dublin, who lead the study.

The findings of the study were published in Molecular Cell.

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