Study Finds Mutation In Colorectal Cancers May Increase Susceptibility to New Cancer Drugs

Study Finds Mutation In Colorectal Cancers May Increase Susceptibility to New Cancer Drugs

shutterstock_117418396A study titled “RNF43 is frequently mutated in colorectal and endometrial cancers” and published in Nature Genetics found a new gene, RNF43 that is frequently mutated in colorectal adenocarcinomas and endometrial carcinomas and has the potential to become a new cancer biomarker.

Studying in vivo mouse models of cancer, the authors found a significant incidence of mutations at the RNF43 gene, accounting for approximately 20% of mutations in colorectal and endometrial cancers and establishing RNF43 as one of the most frequent mutated genes in these types of cancers.

The RNF43 gene encodes a E3 ubiquitin ligase that negatively regulates the Wnt signaling pathway, previously established as playing a role in different forms of cancer. The research team at the Dana-Farber Cancer Institute and the Broad Institute of MIT and Harvard observed that in animal models, tumors presenting RNF43 mutations were responsive to Wnt pathway inhibitors.

Charles Fuchs, MD, MPH, director of the Center for Gastrointestinal Cancer at Dana-Farber and affiliated with Brigham and Women’s Hospital and the Harvard School of Public Health noted in a Dana-Farber news release, “Tumors that have this mutation may be telling us that they are dependent on the Wnt signalling pathway, and they will be uniquely sensitive to drugs that inhibit this pathway.”

The authors analysed 185 colorectal cancer specimens obtained from two preceding cohort studies, the Nurses’ Health Study, comprising 121,000 healthy women since 1976, and the Health Professionals Follow-up Study, that included 52,000 men enrolled in 1986. After finding the RNF43 mutation in 18.9 percent of colorectal patients, they re-analyzed 222 colorectal cancer samples from a previous study and discovered, once again a RNF43 mutation present in 17.6 percent of the samples. Abnormal Wnt signalling was also known to be a cause of endometrial cancer. By re-analyzing 248 DNA samples from endometrial cancer patients, the authors discovered RNF43 mutations were present in 18.1 percent of these cancers.

The team suggested that due to the high incidence of mutations in the RNF43 gene, it had the potential to be used as a new biomarker to identify colorectal and endometrial cancer patients who are suitable to receive anti-cancer therapy targeting the Wnt pathway. Even though such Wnt-targeting drugs are not currently available, their results highlight their potential benefit to this population of patients.

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