Understanding adenoma progression

Colorectal cancer (CRC) affects around 145,000 people a year in the United States and is the third most common cause of cancer related deaths. CRC arises from early lesions that are pre-cancerous; these early lesions are colon adenomas and serrated sessile lesions (SSL).

In light of the well characterized clinical natural history of adenomas, researchers, including Drs. Neelendu Dey, assistant professor, and William Grady, professor (Gastroenterology) plan to study them as early lesions and to determine the mechanisms involved in the formation and progression of early precancerous lesions.

Notably, only a few early adenomas will progress to advanced adenomas (AA) and even fewer will progress to CRC.

"We know from colonoscopy studies that detection of early cancers and precancerous polyps can save lives," says Dey. "So we build on that by asking, what happens at the molecular and cellular level in the so-called 'microenvironment' of the colon in which precancerous and cancerous lesions develop?

We postulate that a set of genetic and epigenetic mutations, changes in cellular behavior (we have a strong interest in 'senescence,' which is a cellular aging phenomenon linked to cancer), and the microbiome are required before precancerous and cancerous lesions develop. We refer to this set of changes as 'priming,' and we aim to better define this so that we can develop tools for detecting colorectal cancer even earlier than we do now."

These studies will integrate basic and translational cancer research projects to iteratively examine the direct causal relationships and interactions of adenomas, the colon “primed” microenvironment, and hostsystemic factors as “co-organizers” of adenoma initiation and/or progression.