Residual EMP1+ Cells Involved in Colorectal Cancer Recurrence

Colon cancer is one of the most common forms of cancer worldwide, with about 2 million new cases each year. Most forms of treatment include surgery and chemotherapy, but 1/3rd of patients have residual tumor cells that are often hidden at the time of surgery and ultimately experience relapse. To better understand why some patients experience relapse and others don't, researchers at the Institute for Research in Biomedicine (IRB) in Barcelona identified how residual tumor cells hide within the liver and lungs and how they metastasize in these organs.

The team, led by the head of the Colorectal Cancer Laboratory at IRB, Dr. Eduard Batlle, developed a new experimental mouse model that chemically mimics the experience of relapsed patients to test out a technique allowing the isolation of small tumor cells hidden in the liver.  

"The model, which is very similar to the progression of metastatic colon cancer in patients, has allowed us to describe the dynamics of residual disease in detail," says first author Dr. Adrià Cañellas-Socias, a researcher at Dr. Batlle's lab. "We have studied metastases ranging from the micro-scale of 3 or 4 cells to medium-sized or even larger ones and have detailed how each of them evolves during the progression of the disease."

While scientists have long known that colon cancer is composed of different types of tumor cells, Dr. Batlle and colleagues identified a specific population that they named High Relapse Cells, or HRCs. These cells do not contribute to the growth of the primary tumor, but they can detach from the tumor and migrate through the bloodstream, reaching regions of the body like the liver. This allows them to remain hidden from the initial tumor site and not be noticed as easily during surgical interventions.

In samples from colon cancer patients, the team verified that these HRCs were present in the individuals with the most significant risk of relapse post-treatment. The team also confirmed that eliminating these cells via gene editing techniques prevented metastases formation in mice. The team also developed an immunotherapeutic strategy to implement prior to surgery that erases residual disease and helps to prevent recurrence.

"Our discovery reveals how the group of tumour cells responsible for relapse behaves and also the genes that define them. In addition, it represents a proof of concept that paves the way for the development of new therapies, specifically aimed at eliminating residual disease, as well as new diagnostic tools to identify those patients at the greatest risk of relapse. Finally, our study points to the need for a revision of the clinical guidelines in the treatment of this type of cancer because, in many cases, it would be advisable to prescribe immunotherapy before surgery," concludes Dr. Batlle.

In the future, the investigators want to focus on how HRCs become "activated" after reaching the liver and how this impacts their ability to regenerate tumors. They hope to learn how to interfere with this process and better prevent the formation of metastases. They also hope to identify factors that influence HRCs' appearance and learn more about why the number of these cells varies so significantly from one patient to another.

Their findings were published in Nature.