Jun 25, 2019 | Updated: 07:39 AM EDT

Researchers Restored Silenced Cancer Genes to Fight a Broad Range of Cancers

Apr 15, 2019 10:48 AM EDT

Researchers Restored Silenced Cancer Genes to Fight a Broad Range of Cancers
(Photo : Image by PublicDomainPictures from Pixabay)

After a due study of human colon cancer cells and mice, John Hopkins Kimmel Cancer Center researchers and experts confirm that they have successfully blocked the activity of portions of a protein referred to as UHRF1 and restored the function of hundreds of cancer-fighting genes that became misregulated by the disease.

The investigators confirm, in a report on the research published online in Cancer Cell, that the discovery could lead to an entirely new strategy to fight a broad range of cancer.

Stephen Baylin, the study leader, and D. K. Ludwig said that researchers have known that gene mutations can cause cancers. Recently, it became clear, however, that faulty gene regulation can also maintain and prompt the disease. Through a process known as epigenetics, the other phenomenon can happen whereby chemical tags settle onto genes to turn them on or off.

A methyl group which is one type of chemical tag typically silences the function of gene once the cells clip it. Cancers harness this type of epigenetic regulation to broadly turn off genes that cells regularly use to fight the onset or growth of cancer.

There have been some attempts by the researchers to adopt this strategy to the treatment of cancer by developing drugs that knock off methyl groups to turn cancer-fighting genes back on. Baylin explained that it had been a challenge to produce medicines that robustly penetrate solid tumors and effectively remove methyl groups simultaneously. As a result, drug s like 5-azacytidine and entinostat haven't yet been as effective as researchers have hoped especially in solid tumors.

In a new way to influence the epigenetics of cancer, Baylin and colleagues from the Van Andel Research Institute and Tongki Medical College in China turned to UHRF1. Even when they know that this protein is responsible for adding and maintaining methyl groups, Baylin explains that they have never explored it entirely as a way of blocking methylation and make it a potential drug target.

Also for them to better have a grasp of how UHRF1 operates, they devised an experiment that allowed them to block discrete parts of this protein in human colon cancer cells with established abnormal methylation patterns. The outcomes revealed that two distinct segments of the protein were pivotal in helping cells maintain these unusual patterns. One of them is plant homeodomain (PHD) and another called SET and RING-associated domain (SRA).

In the end, Baylin and his collaborators discovered that repressing those two key domains could offer a new way of controlling cancers. The researchers are working with a company to develop a drug to accomplish this goal, either alone or in combination with existing drugs. Since methylation patterns go awry almost universally in cancer, Baylin added that such a drug could help fight a wide range of cancer types.

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