The latest research has shown that epigenetic pathways may provide new therapeutic options for patients with cancer. Researchers know that changes in epigenetic control of gene expression in cancer cells, and surrounding cells in the tumor microenvironment, play a fundamental role in driving tumor development, as well as response to chemotherapy and immune treatment.

Wendy Henderson, CRNP, MSN, PhD, from the division of intramural research at the National Institute of Nursing Research National Institutes of Health Department of Health and Human Services, and Peter Jones, PhD, DSc, of the Van Andel Research Institute, discussed epigenetic pathways and how to target them via new treatment options during a session at the 41st Annual Congress in San Antonio, TX. The session was jointly sponsored by the American Association for Cancer Research and ONS.

Jones began the session with some background information on epigenetics, specifically how chromatin impacts the epigenome. “If you look to chromatin in the cancer cell, it is different,” he explained, noting that the discovery of abnormal chromatin will lead to a diagnosis of cancer. 

He explained that the genes a person inherits do not show the complete picture for why some people develop cancer and other do not. For example, in a set of identical twins—with the same genes—one can develop cancer while the other does not. Jones said that a person’s lifestyle factors, such as diet and exercise, as well as others, can impact the epigenome, which can get misaligned and can ultimately lead to cancer.

Recent advances in the cancer space have indicated that genes get turned off, and they need to be turned back on to treat cancer. This is seen in the newer immunotherapy drugs. “What is really important is that the gene is still there. It is off. But if we can figure out how to switch it back on, you might be able to use that in treatment,” Jones said. 

Epigenetic therapy along with chemotherapy or immunotherapy may be the future of treatment cancer. “Using combination therapy is going to be the way we need to go,” Jones said. “Given the uptick in immunotherapy, image if we could turn on these genes. It would increase the efficacy of these drugs.”

Jones went on to discuss The Cancer Genome Atlas (TCGA), a National Institutes of Health initiative, which is a comprehensive and coordinated effort to accelerate the understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing. So far, TCGA has examined genes in 10,000 human cancers. 

Henderson continued the presentation by discussing her research, which focuses on how stress affects intestinal health. She began by noting some key facts about stress, including that up to 20% of the U.S. population reports stress-induced gastrointestinal (GI) symptoms. GI complaints are the single most common reason for emergency visits and in the top 10 reasons for outpatient visits. GI issues are associated with $30 billion in healthcare costs annually, and research evidence supports the notion that chronic stress affects intestinal health across the lifespan. 

Henderson noted that her research findings in chronic stress and its relation to the brain-gut-microbiome axis could be applied to epigenetics to fuel cancer research. Through her study, published in Biological Research for Nursing, she explained the correlation that stress affects intestinal permeability, which leads to translocation and ultimately results in abdominal pain. The purpose of the study was to examine the expression genes involved in stress and toxicity in men and women with high and low levels of perceived stress, with and without chronic abdominal pain. 

After analyzing laboratory and mice models, the research team used cancer cells and tested the permeability with transepithelial electric resistance and found, “There’s a clear effect of chronic stress in this cancer model,” Henderson said.

“An upregulation of the gene coding the proinflammatory cytokine interleukin-1α suggests that the mechanism behind stress-related changes in GI symptoms is pro-inflammatory in nature,” the study authors concluded.

“Find ways to quantitate what the patients tell you to find things that are unknown,” Henderson concluded. She encouraged the audience to discover other models, perhaps not related to oncology, to support their findings and look to other resources that can help propel cancer research and breakthroughs.

Henderson, W., & Jones, P. (2016). American Association for Cancer Research/ONS session: Epigenetics and cancer. Session presented at the ONS 41st Annual Congress, San Antonio, TX, April 28, 2015. 

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