They discovered a new regulator of the p53 protein that could open up new therapeutic options for treating cancer.

p53 is the cornerstone of cellular genomic stability. If a cell has damaged DNA, it needs p53 to activate an effective repair program. Regulation of p53 has been studied extensively at the protein level, but this new project examines how its activity is controlled by messenger RNA, which contains information about the production of the p53 protein.

An innovative approach to studying p53

This study shows that the YTHDC1 protein helps regulate both the expression of the p53 messenger RNA and other genes required for the proper detection and repair of DNA damage. Moreover, it was found that this mechanism is associated with both transcription and the correct processing of messenger RNAs. “Although this processing depends on chemical modifications of the RNA, transcriptional regulation does not appear to depend on them. This suggests that YTHDC1 acts at multiple levels to mediate the cell’s response to damage to its DNA, helping both to activate p53 and to process other RNAs needed for DNA repair. This discovery prompts us to explore how we can use this protein as a therapeutic target in the treatment of cancer,” explains Dr. Maite Huarte, DirectorDNA and RNA Therapy Division of Cima.

As he explains, “There is a correlation between tumor genomic instability and response to both chemotherapy and immunotherapy. Tumors with greater genomic instability respond best. “This could be a possible avenue to explore.” The results were published in the scientific journal EMBO Journal.

For her part, Dr. Daniel Elvira Blazquez, first author of the project, adds: “We know that YTHDC1 is involved in many diseases, and we are now focused on developing specific inhibitors that can enhance the genomic instability of tumors, making them more effective.” sensitive to treatment.”

Future prospects and clinical applications

The results open the door to new therapeutic strategies, especially for cancers such as lung cancer. By increasing the genomic instability of tumors, they become more sensitive to immunotherapy and chemotherapy. The research team will continue to search for specific YTHDC1 inhibitors with the goal of developing more effective therapeutic combinations in the near future.

Discovery of this p53 regulator may supportThis represents significant progress in cancer treatment and an important step towards personalized medicine in the fight against this disease.