Due to the limited effectiveness of existing therapies, colorectal cancer remains the third leading cause of cancer death in Western countries. According to national statistics, the probability of developing this form of cancer during one's lifetime exceeds 5% for men and 3% for women, accounting for more than 12% of all cancer diagnoses. Despite advances in early diagnosis and treatment, the mortality rate remains significant at around 35%.

A study, a collaboration between Sapienza University and the University of Palermo and published in the journal Molecular Cancer, revealed a mechanism that allows colorectal cancer to evade the body's natural defences, making it more difficult to treat the disease. Specifically, the researchers identified how the SETD8 enzyme, known to promote the formation of several types of tumour, inhibits the action of the p53 protein, an important natural barrier against tumour growth. This mechanism is particularly triggered in cancer stem cells and macrophages, immune cells that in some cases can promote cancer proliferation.

‘The discovery opens up new therapeutic perspectives: reactivating the p53 protein could be an effective strategy to block tumour growth,’ say Veronica Veschi of Sapienza University, Matilde Todaro and Giorgio Stassi of the University of Palermo. ‘Moreover, the study suggests that new drugs targeted against this mechanism could be used alone or in combination with existing therapies, thus improving the treatment possibilities not only for colorectal cancer but also for other inflammation-related neoplasms’.

The study was carried out thanks to the contribution of AIRC, funding from the National Recovery and Resilience Plan for Precision Medicine, and funds from the Department of Molecular Medicine of Sapienza University as a Department of Excellence, involving a multidisciplinary team of national and international experts, such as Ettore Appella. Alongside Sapienza and the University of Palermo, the project leader, the research comprised other Italian and international institutes: VillaSofia -Cervello Hospital and the Policlinico ‘Paolo Giaccone’ in Palermo, the IRCCS Regina Elena in Rome, Queen Mary University in London and the National Cancer Institute, National Institutes of Health in Bethesda, Maryland, USA. The results represent a step forward in understanding the molecular mechanisms underlying cancer and offer new hope for patients suffering from this disease.

References:

Veschi, V., Verona, F., Di Bella, S. et al. C1Q+ TPP1+ macrophages promote colon cancer progression through SETD8-driven p53 methylation. Mol Cancer 24, 102 (2025). https://doi.org/10.1186/s12943-025-02293-y

Further Information

Veronica Veschi

Department of Molecular Medicine

veronica.veschi@uniroma1.it