Colorectal cancer, intestinal carcinoma, colon cancer, bowel neoplasia, 3D illustration
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Scientists at the Institute for Research in Biomedicine (IRB), in Barcelona have identified residual tumor cells responsible for colon cancer relapse and reveal the underlying mechanism behind their ability to metastasize.

In the United States, colorectal cancer is the third leading cause of cancer-related deaths in men and women with over 100,000 new cases in 2022 alone. The regular treatment for patients before apparent metastasis involves removal of primary tumors by surgery and additional chemotherapy to prevent relapse. However, relapse rates continue to stay relatively high with 30% to 40% of patients developing metastatic tumors in other organs after treatment.

Reporting in Nature, researchers at IRB have now developed a new experimental animal model aiming to recreate the process of colon cancer relapse in patients. Using their model, and a parallel technique, the scientists were able to isolate tiny amounts of residual colon cancer cells that had traveled and hidden in other organs such as the lung and liver making themselves invisible to current clinical diagnostic tools.

“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,” said  Adrià Cañellas-Socias, PhD, postdoctoral research fellow at the IRB and first author of the study.

The scientists were also able to characterize a population of cells driving colon cancer as High Relapse Cells (HRCs). These cells reportedly do not contribute to the growth of the primary tumor due to little proliferative activity. However, clusters of these cells are able to detach from the tumor and migrate via the bloodstream to other organs such as the liver, where they remain hidden after surgery. Using samples from patients with colon cancer, the researchers verified the presence of HRCs in patients with the greatest risk of relapse.

In an attempt to eliminate HRCs, the researchers removed the cells in mice models using genetic techniques, achieving the prevention of the formation of metastases. Mice with colon cancer remained disease-free after primary tumor removal and the cancer did not recur. The team also demonstrated that treatment with immunotherapy before surgery can remove HRCs that have traveled to other organs, eradicating residual cancer.

“Our discovery reveals how the group of tumor 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,” concluded Eduard Batlle, PhD, head of the colorectal cancer laboratory at the IRB and senior author of the study.

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