A mechanism to stop lethal childhood cancer

A mechanism to stop lethal childhood cancer
 

Malignant rhabdoid tumor (MRT) is one of the most aggressive and lethal childhood cancers.

Although rare -- about 20 to 25 new cases are diagnosed annually in the United States -- there is no standard effective treatment for the disease, which is driven by loss of an anti-cancer protein called SNF5. The chances are very small that a child will survive a year after MRT diagnosis.

Now researchers have discovered that a pro-cancer protein, MYC, is normally inhibited by SNF5. Loss of SNF5 effectively "takes the brakes off" MYC, thus accelerating cancerous growth.

Reporting in the journal Nature Communications, the researchers conclude that blocking MYC could be "unexpectedly effective" in treating MRT as well as other cancers driven by inactivation of SNF5.

"One of the difficulties in treating a cancer like MRT is that it's driven by the loss of a particular protein from the tumor cell," said the senior author.

"Showing that MYC is activated by SNF5 loss identifies a target you can conceivably go after in these cancers," said the author.

MYC proteins function as transcriptional regulators, controlling the expression of thousands of genes linked to cell growth, proliferation, metabolism and genomic instability. The lab is focused on determining basic mechanisms of MYC action that can lead to new strategies to target MYC in the clinic.

Using biochemical and genomic approaches, researchers demonstrated that SNF5 selectively inhibited binding of MYC to DNA, something that is required for its tumorigenic function. Authors show that MYC regulation by SNF5 is separable from its role in chromatin remodeling, and that reintroduction of SNF5 into MRT cells also displaced MYC from chromatin (the complex of DNA, RNA and protein that form chromosomes), inhibiting pro-cancerous gene expression programs.

https://www.nature.com/articles/s41467-019-10022-5

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Finhibition-of-myc-by&filter=22

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