Home Science New molecule chops up RNA of “undruggable” common cancer-causing gene

New molecule chops up RNA of “undruggable” common cancer-causing gene

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New molecule chops up RNA of "undruggable" common cancer-causing gene

A gene called MYC is implicated in the majority of cancers, but unfortunately it’s often considered “undruggable.” In a new study scientists have developed a molecule that chops up the RNA of this gene, effectively clearing cancer in mice.

The MYC gene plays a key role in regulating cell proliferation, metabolism and controlled cell death, but it’s not always helpful. In fact, it’s been implicated in as many as 70% of all human cancers, covering a wide range of types of the disease, and overexpression is associated with worse outcomes for patients.

That makes it an attractive target for treatment, but unfortunately it’s not that simple. The associated MYC protein has a strange shape that makes it hard for drug molecules to latch onto, leading it to be considered mostly undruggable.

But a new study might be a step towards changing that. Researchers at The Wertheim UF Scripps Institute, Max Planck Institute and the University of Münster have developed a way to bypass the tricky protein and shut down the gene by instead targeting its messenger RNA (mRNA). These molecules transcribe DNA to produce proteins, so interrupting that process can prevent the proteins being made rather than inactivating those already produced.

First, the team designed compounds made from imidazole that strongly bound to the mRNA of the MYC gene, as well as two other RNAs linked to cancer, JUN and microRNA-155. Binding alone didn’t seem to help much, so the researchers added an extra structure to their molecules. This was designed to work like a fishing hook to catch enzymes that recycle RNA, and direct them to degrade the attached RNA. And sure enough, early results looked promising.

“With the degrader added, we started seeing these ‘undruggable’ cancer RNAs reduced by 35%, 40%, 50% or more,” said Matthew Disney, lead author of the study. “This caused cancer cells to die and cleared tumors in mouse-based studies of breast cancer that spread to lungs.”

Of course, it’s still very early days for the technique, and the researchers say they still have a “marathon” ahead of them before it could reach human clinical trials. But it adds new hope for future treatments of many human cancers and other diseases.

“The compounds are a good starting point and show us where to go to build small molecules, RNA-targeting medicines that could eventually treat patients with diseases like aggressive cancers that currently have poor or no options,” said Disney. “This new data also shows us that this approach could have many other disease applications.”

Other scientists have had some success treating this undruggable cancer gene by going after different targets, including downstream proteins or suppressing the MYC gene itself.

The new research was published in the journal Nature.

Source: Max Planck Institute

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