A team of researchers from Fred Hutchinson Cancer Research Center has identified a gene that could make immunotherapy treatments (checkpoint inhibitors) help an even wider group of cancer patients. The team in Seattle found that when the DUX4 gene is expressed in cancer cells, it might be able to prevent cancer from being recognized and extinguished by the immune system.
Who Led this Effort
What is DUX4
The DUX4 gene is located near the end of chromosome 4 in a region known as D4Z4. This region consists of 11 to more than 100 repeated segments, each of which is about 3,300 DNA base pairs (3.3 kb) long. The entire D4Z4 region is normally hypermethylated, which means that it has a large number of methyl groups (consisting of one carbon atom and three hydrogen atoms) attached to the DNA. The addition of methyl groups turns off (silences) genes, so hypermethylated regions of DNA tend to have fewer genes that are turned on (active). Interestingly, the gene is mostly known for its link to specific muscular dystrophy.
What did the Research Team Find?
While they were analyzing gene expression profiles of almost 10,000 cancers with 33 cancer types they discovered that DUX4 consistently presented itself in many different solid tumors including bladder, breast, lung, kidney and stomach cancers reported ScienceDaily. It was observed in ScienceDaily that DUX4 is a gene mostly known for a link to a specific muscular dystrophy (facioscapulohumeral dystrophy, or FHSD) “consistently presented itself in many different solid tumors, including cancers of the bladder, breast, lung, kidney, and stomach. DUX4 prevented immune cells from recognizing the cancer cells so that patients whose cancers expressed the gene were less likely to respond to immunotherapy. Because DUX4 is expressed in many cancers, blocking its activity might increase the success of immune checkpoint inhibitors.”
What do the Findings of the Study Suggest?
Investigator Stephen Tapscott declared “This study suggests that cancer cells express DUX4 to hijack a normal early developmental program that can suppress anti-cancer immune activity.” He further noted that individuals with FHSD don’t have increased cancer risk, indicating the cancer cells are using DUX4 as a developmental tool to avoid the immune system, but not as a driver that causes cancer.
Goal: DUX4-Targeted Treatments
Both Robert Bradley and Stephen Tapscott hope that this early-stage research could lead to the development of DUX4-targeted treatments will enhance the success of immunotherapies for a broad range of cancers.