Researchers find cells that cause relapse of colon cancer

Colon cancer is the third most common disease in the world, with more than 2 million new cases diagnosed each year. Most individuals find out they have a tumour while it is still in the colon or rectum.

In an effort to prevent a relapse, these tumours are surgically removed and frequently treated with chemotherapy. However, between 20 per cent and 35 per cent of people experience cancer coming back as metastases in other important organs. These are caused by tumour cells that are still there but are not visible when surgery is performed. The most frequent cause of death from almost all cancers, including colon cancer, is metastasis.

The majority of colorectal cancer research has concentrated on the main condition. Additionally, there have been significant developments in recent years regarding how to identify metastatic disease after it has already manifested.

But up until recently, it had been impossible to investigate this small group of disseminated tumour cells since they are undetectable by clinical diagnostic methods. Because of this ignorance, there aren't many medications that can effectively treat the remaining disease and stop it from spreading again, which has a bad prognosis.

Scientists at IRB Barcelona, led by Dr Eduard Batlle, ICREA researcher and group leader within the cancer CIBER network (CIBERONC), have for the first time identified residual tumour cells hidden in the liver and lung and have described how they evolve to give rise to the appearance of metastases in these organs.

"Understanding and avoiding the phenomenon of relapse after surgery is an unresolved medical need. After many years investigating colon cancer, we have taken the first step to prevent metastases in patients who present with localized disease," explains Dr Eduard Batlle, head of the Colorectal Cancer Laboratory at IRB Barcelona.

How does colon cancer recurrence occur?

A novel experimental mouse model that mimics the process patients go through when they relapse has been created by scientists. The typical progression of this is the diagnosis, curative surgery, and relapse. In addition, they have developed a method that enables the isolation of a minor portion of liver-hidden disseminated tumour cells.

"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. 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," comments Dr Adria Canellas-Socias, a researcher at the laboratory headed by Dr Batlle and first author of the study.

Defining the High Relapse Cells

As the disease advances, different tumour cell types that makeup colon cancer each carry out a certain function. This is something that scientists have understood for a long time. Numerous cell types can cause colon cancer, and Dr Batlle's team of researchers has identified a subset of these cells as HRCs (High Relapse Cells). These cells rarely divide and do not aid in the progression of the underlying tumour. Although they can move to the liver and remain hidden for some time after surgery, HRC clusters have the ability to split off from the underlying tumour. In samples from colon cancer patients, researchers have been able to confirm the presence of these identical cells in those who are most at risk of relapse after treatment.

Additionally, researchers have shown that eliminating these cells via genetic techniques is sufficient to prevent metastasis, as shown by the fact that colon cancer in mice does not return after the initial tumour has been removed. Additionally, Dr Batlle's team has developed a treatment strategy to specifically get rid of any disease that may still be present and prevent it from coming back. They have demonstrated that early-stage, imperceptible metastases can be eliminated by immunotherapy before surgery.

"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.

New research directions may be developed in light of these findings. In order to thwart this process and stop the growth of metastases, Dr Batlle's lab is now concentrating on understanding when HRCs that have entered the liver become "activated" to regenerate a tumour. They are also trying to figure out what influences how these cells look and why different patients have different numbers of these cells.

( With inputs from ANI )

Disclaimer: This post has been auto-published from an agency feed without any modifications to the text and has not been reviewed by an editor