Colon cancer is the third most common and second most lethal cancer in the United States. The only effective treatment for this cancer is surgery, and the immunotherapies that have transformed the way advanced cancer is treated have only been effective in a limited percentage of colon cancer patients. Because of this, it is very important to find new targets as soon as possible.

Researchers at the Tisch Cancer Institute of Mount Sinai have uncovered a new gene that is crucial for the growth of colon cancer and discovered that inflammation in the external environment surrounding the tumor can contribute to the growth of tumor cells. 

The researchers published their findings in Nature Communications.

It is the first time researchers have discovered that the environment around a colon cancer tumor can program a “super enhancer,” a complex area of DNA with a high concentration of transcriptional machinery that controls whether or not a cell is cancerous.

The PDZK1IP1 gene, which was not previously recognized as a cancer gene, is controlled by this super enhancer, which is the biggest 1-2% of all enhancers in the cell. Deleting PDZK1IP1 decreased the progression of colon cancer, suggesting that PDZK1IP1 and its super enhancer could be therapeutic targets.

“In the United States, colon cancer is the third most prevalent and second most deadly cancer,” says first author Royce Zhou. “This cancer is reliant on surgery for treatment, and immunotherapies that have revolutionized the treatment of advanced cancer have only worked for a small subset of colon cancer patients. That’s why there’s a great need for novel target identification.”

According to the findings of this study, the super enhancer is turned on when there is inflammation present in the microenvironment of the tumor. The cancer cells can live in an environment where they otherwise wouldn’t be able to because of the inflammation. Colon cancer is known to be linked to inflammatory bowel disease. This finding could help us figure out how that happens.

“What this means for most patients with colon cancer is that inflammation that’s occurring in the tumor is contributing to the tumor’s growth. This stresses the importance of understanding what we can do to curb the inflammatory effects in the colon through prevention or understanding what dietary effects might have on the microenvironment in the colon,” adds senior author Ramon Parsons. “In terms of treatment, we have genetic evidence that targeting this gene actually inhibits tumors. By understanding all these different components, we will have better tools to try to prevent the disease.”

This result was made feasible by the examination of live tumor tissue and surrounding healthy tissue immediately following the surgeries of fifteen colon cancer patients. Mr. Zhou explained that the ability to prepare and study living cells enabled researchers to observe the tumor microenvironment and the genetic and biological drivers of colon cancer.

“We had live specimen live cells straight from the operating room that allowed us to immediately measure the epigenetic state of that tumor,” Dr. Parsons adds. 

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