How do molecular ‘switches’ impact colorectal cancer? And what could they mean for treatment?

Throughout our lives, we’ve been reminded that eating a nutritious diet is important for our overall good health and helps reduce the risk of many cancers, including colorectal cancer.

But there also are many risk factors that are simply part of us. The most familiar are genetics and family history. One you might be less familiar with is epigenetics. Epigenetics is a complex set of processes that determine when and to what extent certain genetic instructions are carried out. Epigenetic processes are essential for healthy cellular function. However, when things go awry, they can play major roles in disease.

One epigenetic process is known as methylation, which acts like a switch that tells the body’s cellular machinery when specific genes should be turned on or off. In cancer cells, these patterns change, impeding the normal checks-and-balances on cell growth and allowing malignant cells to flourish and spread. UHRF1 is a protein involved in epigenetics — a key regulator of biological processes— that can drive colorectal and other cancers. In fact, research from the Rothbart Lab at Van Andel Institute has shown that blocking specific parts of UHRF1 switches on hundreds of cancer-fighting genes, impairing cancer’s ability to grow and spread.

Understanding all the various factors that influence colorectal cancer is crucial. Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States (excluding skin cancers). It’s estimated that 151,030 men and women will be diagnosed with colorectal cancer in 2022. And this year, colorectal cancer is also projected to take the lives of 52,580 men and women in the U.S., the second leading cause of cancer-related death for men and women combined.1 Rates of colorectal cancer also are rising in younger people who haven’t yet reached the age in which regular screening is recommended. 2

VAI researchers continue to study the role of UHRF1 in an effort to develop new, improved inhibitors to treat colorectal cancer. They’re exploring whether medications that target other epigenetic factors may be a viable approach for better treating the disease. And they hope to leverage molecular profiling of epigenetic processes to help better identify colorectal cancer subtypes and disease stages, improving physicians’ ability to take a personalized approach to treatment.

To learn more about colorectal cancers, visit: vai.org/colorectal-cancer-month-explainer.



1 American Cancer Society. 2022. 2022 estimates. https://cancerstatisticscenter.cancer.org/?_ga=2.239342531.1759875586.1646672622-244632275.1646672621#!/

2 Simon S. 2020. Colorectal cancer rates rise in young adults. American Cancer Society. https://www.cancer.org/latest-news/colorectal-cancer-rates-rise-in-younger-adults.html