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Patients resistant to breast cancer therapy show epigenetic differences

Patients resistant to breast cancer therapy show epigenetic differences

Low levels of methylation of DNA (hypomethylated state) in promoter regions enable binding of transcription factors (TFs), leading to gene activation and later protein production. Increased DNA methylation (hypermethylation) in promoter regions inhibits binding of transcription factors (TF) resulting in reduced gene activation and thereby reduced protein production. Credit: Daniela Furrer, University of Laval

According to a new study, breast cancer patients who do not respond to targeted therapy have different forms of epigenetic modification from responding patients. Epigenetic changes alter the gene expression without altering the genetic DNA code.

"Our research could contribute to new ways of predicting who can not respond to targeted therapy," said Dr. Sc. Daniela Furrer, Postdoctoral at the Laval University, Canada, who conducted the research. "This could also lead to a way to identify patients who need closer clinical monitoring because they are more prone to breast cancer return."

Furrer will present a research at the annual US Society of Investigative Pathology meeting during a 2019 experimental biology meeting that will take place from 6 to 9 April in Orland, Fla.

Targeted cancer therapies use drugs to block molecules in cells that cause it to grow out of control. Therapy specifically targets cancer cells, unlike chemotherapy, which kills all fast growing cells, whether they are carcinogenic or not. Although development of targeted therapies has increased breast cancer survival, treatment failure is still an important issue.

"This is one of the first studies to assess the impact of epigenetic modification on treatment response to targeted therapy in subgroups of breast cancer patients," Furrer said. "It's important that we measured these changes directly in the breast cancer tissues and reviewed the epigenetic modification across the entire breast cancer cell."

For a new study, researchers investigated the type of epigenetic change known as DNA methylation in breast cancer patients from HER2-positive breast cancer patients who received the targeted drug trastuzumab (Herceptin). Trastuzumab targets the growth factor epidermal growth factor receptor (HER2) receptor, which promotes cancer cell growth.

The researchers compared the patterns of methylation of DNA to six patients who responded to the therapy, and six to those who did not. Tumor Tumor Cancer from therapy-resistant patients showed 879 genes with higher methylation levels and 293 with lower methylation than patients who responded to treatment. Many of the genes affected were involved in cellular motion, as well as cell death and survival, processes that play an important role in cancer.

The next step in this research is to confirm findings in a larger group of breast cancer patients receiving targeted treatment. If the findings are confirmed, researchers plan to develop new drugs targeting molecular pathways and cellular processes that lead to targeted failure of DNA methylation treatment.

A new insight into aggressive forms of breast cancer

More information:
Daniela Furrer will present this research on Saturday, April 6 at 7 pm. during the reception of experimental biology in Valencia at the ABCD Hall, at the Orange County Convention Center and on Monday, April 8 at 9:45 am in Room W108 B (poster 250.6) (abstract).

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