A team of researchers from the Institute of Genetic and Biomedical Research of the National Research Council (Cnr-Irgb) of Milan, in collaboration with Humanitas, carried out aor groundbreaking study on cellular aging and its relationship to colon cancer. The phenomenon of cellular aging, known as cellular senescence, was analyzed in biopsies of liver metastases from patients with primary colon cancer. The aim of the work was to understand the role of this process in the advanced stage of the disease.
The result of this research, which was published and earned the cover of the magazine Aging Cellrevealed the presence of two types of senescent cancer cells with completely opposite effects. One category of senescent cells was shown to be benign, while the other was malignant, with different impacts on patient survival and recurrence times after surgery. To oversimplify, senescent cancer cells actually divide into good and badand the possibility of recognizing them and working on the two groups separately underlies the importance of this study.
Research
Colon cancer is often associated with the formation of liver metastases, which pose a significant clinical challenge. Liver metastases occur in 50% of patients and are responsible for 90% of cancer mortality. Currently, surgical removal after neoadjuvant chemotherapy is the standard treatment, but only a small percentage of patients are eligible for this type of surgery. This is due to poor understanding of the evolutionary process of the disease and the dynamics within secondary organs.
Using an innovative technology called “spatial transcriptomics“, the research team was able to analyze the gene expression of all the cells present within the metastases. The results allowed us to establish how senescent cells have a different impact depending on the pathological context. In some cases, these senescent cells can act in a positive way, stopping the dissemination of the tumor. However, under other circumstances, they develop properties that promote the aggressiveness and advancement of cancer cells.
The results of the study were further validated on a group of seventy metastatic patients, divided according to the type of chemotherapy received. The malignant senescent cells were found to be sensitive to chemotherapy and helped create an immune environment conducive to tumor growth. On the other hand, a higher accumulation of benign senescent cells has been associated with better survival and a more efficient immune environment with antitumor action.
New perspectives of care
These results – defined by revolutionary scholars – could open up new perspectives for the treatment of colon cancergoing beyond the targeting of proliferating tumor cells. Scientists are now planning further research to better understand the mechanisms of metastasis and to explore the use of agents”senolithic“, capable of selectively eliminate senescent cells. This study represents a significant step forward in the fight against cancer and could lead to new targeted and effective therapies for patients affected by this devastating disease.