Colon cancer (CC) is one of the most important neoplasms in terms of incidence and lethality: it has the highest incidence in Spain with more than 45,000 new cases per year and around one million worldwide, and is the second leading cause of cancer death after lung cancer. Survival in CC depends to a large extent on the stage of the disease at the time of diagnosis. Thus, patients with stage I CC have a 5-year survival rate of over 90%. This rate drops to 72-83% in stage II patients and 44-83% in stage III patients. In patients with metastatic CC, the survival rate is low, 24% at 36 months and 13% at 5 years. Metastasis is responsible for the death of the vast majority of CC patients and it is therefore essential to advance our understanding of the molecular mechanisms that govern metastasis.

Understanding the mechanisms involved in the generation of metastases in patients with CC, particularly in early stage patients, is essential for prevention and early diagnosis. There is a real need for good prognostic biomarkers for a correct stratification of stage II patients if we take into account that approximately 20% of stage II patients will develop recurrence during their lifetime and, probably, metastasis.

The microbial ecosystem of the digestive tract, the intestinal microbiota, is part of the tumour environment and is highly relevant in CC. Carcinogenic effects are attributed to Fusobacterium nucleatum, Bacteroides fragilis and some lineages of Escherichia coli. In addition, the presence of F. nucleatum within metastases suggests that it may contribute to their metabolic reactivation. For the development of CC, beyond the composition of the microbiota or the toxins produced, their metabolic products are of particular interest, especially those that may exert their action in remote sites or participate in the interaction with the immune system, such as trimethylamine N-oxide (TMAo) and short-chain fatty acids (acetate, propionate and butyrate).

Objective

The overall objective of the project is to carry out an exhaustive study of the main current challenges in the diagnosis and treatment of CC, taking advantage of the experience and resources of the five groups that form part of the consortium to undertake a joint and cohesive project that includes tasks that, individually, the groups would not be able to tackle. The increase in critical mass will result in greater synergy and will facilitate obtaining a greater scientific-technological impact of the results obtained.

Specifically, the project aims to study in greater depth such relevant aspects as the role of the tumour microenvironment and the intestinal microbiota in the progression of CC, the combination of organoids and animal models in the study of metastasis, the obesity-diabetes-CC axis and the development of new approaches (radiomics and artificial intelligence) that lay the foundations for the implementation of new care tools to improve the clinical management of patients, especially metastatic patients, increasing their life expectancy and quality of life, and ultimately advance in the knowledge and treatment of this neoplasm. We seek to approach the treatment of the patient individually and not the disease in a generalised manner, promoting precision medicine in patients with cancer, facilitating potential technology transfer to interested companies and active dissemination among patient associations.

Adequacy and relevance

This project aims to bring basic and translational research directly from the laboratory to the patient. To achieve this goalThe consortium is made up of a combination of basic and clinical research groups, some of them related to the hospital environment, companies and patient associations, which ensure an integrated and innovative proposal with results that can be easily transferred to the National Health System.

The relevance of this project is evident if we take into account the high incidence and mortality of CC, the most frequent in the Community of Madrid and in Spain, taking into account both sexes together. Furthermore, in this project places special emphasis on metastatic CC, the main cause of death from this neoplasm.