A New Ultra-Rare Form of Cancer?

via Joshua E. Cogan

Researchers at the National Human Genome Research Institute (NHGRI) have identified several novel genes associated with the ultra-rare Erdheim-Chester disease (ECD) which might help to inform future drug therapies. Their findings, collated from data collected between 2011 and 2015, were published in Blood Advances.

ECD affects around 600 people globally and is characterised by the accumulation of histiocytes, a specialised type of white blood cell, in organs and tissues throughout the body. Histiocytes are normally produced to destroy foreign material in the body and help prevent infection as part of the immune system, but in ECD they build up and damage the surrounding tissues, resulting in inflammation. The damage caused by this inflammation leaves the tissues denser, thicker, and scarred, impacting their function.

While ECD has no standard treatment, consensus clinical guidelines were published in 2014 to direct medical care. The most common drug currently being used to treat the disease is the anti-cancer agent interferon, which compromises cell division and thereby limits tumour growth. However, even with treatment, ECD has an estimated 60% mortality rate 3 years after diagnosis.

This study was designed to build a better understanding of the disease so that clinicians would have a clearer idea of how to treat their patients.

“The discovery of new genes associated with ECD provides hope for improving the diagnoses of a disease that affects so many parts of the body. We also hope it will help us identify new treatments,” said Juvianee I. Estrada-Veras, M.D., Clinical Investigator and Staff Clinician at the NHGRI. “Our work on ECD builds on the institute’s goals to advance medical knowledge about rare diseases and to potentially provide insights into more common disorders.”

The researchers investigated 60 adults with ECD at the NIH Clinical Centre. 59 of these samples were available for molecular testing, and upon testing they revealed that half had mutations in the BRAF V600E gene and others had mutations within the genes of the MAPK pathway. Previous work has demonstrated that the BRAF V600E mutations also occur in colon, lung, thyroid, brain, and blood cancers. The MAPK pathway is involved in cell growth and proliferation processes, and mutations within the pathway have also been found in several different forms of cancer.

The team have argued, therefore, that despite the lack of metastasis and the presence of inflammation, that ECD should be classified as a form of cancer. Anti-cancer drugs have already been developed to target MAPK mutations and the researchers have theorised that these compounds may be of use in treating ECD as well.

The research is already being put into effect. Clinical trials for dabrafenib and trametinib, both drugs that target MAPK, have now been opened to patients with ECD who have mutations within the BRAF V600E gene.

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