VHIO’s Colorectal Cancer Group has extensive experience in managing this disease. The group leads and actively partners in different clinical and translational research programmes whose aim is to identify prognostic/predictive response markers to be able to differentiate more accurately between patients who will or will not benefit from the treatments, and to investigate the mechanisms responsible for acquiring therapeutic resistance.

The group can be considered a pioneer in the use of liquid biopsy in the treatment of colorectal cancer (CRC). The group has taken part in studies aimed at validating the prognostic worth of ctDNA, and specifically of FAM (RAS mutated allelic fraction, FAM-RAS), with the aim of identifying higher-risk patients and implementing more optimal treatments.

In the last few years, the group has been consolidated as a benchmark in the subtype of tumours with mutation in the BRAF gene. This mutation presents with clinicopathological and molecular characteristics, such as mucinous differentiation and a higher incidence of microsatellite instability, resulting in an aggressive phenotype with poor prognosis. The research into this subtype has proven highly productive, a highlight of which was the group’s participation in the prestigious BEACON phase III clinical trial, whose results led to the approval of the BRAF inhibitor, encorafenib, together with cetuximab, in patients with CRC with the BRAFV600E mutation. As a continuation of this line of research, the group is leading different translation research projects and academic clinical trials with the aim of identifying new mechanisms of resistance and new treatments to improve patient treatments.

One of the lines of research we intend to consolidate in the coming years is the study of young patients diagnosed with CRC due to the growing need to specifically address this type of patient, given that its incidence has increased throughout the world in recent years. The reasons for this increase are not entirely clear, but it is likely that there is a direct relationship with the set of exposures and interactions the individual is subject to throughout their life (exposoma). These exposures not only cause genetic and epigenetic alterations in colorectal epithelial cells, but can also impact on the gut microbiota and host immunity. The aim is to understand the mechanisms involved in the pathogenesis of CRC in young patients.

Also connected to this line of research is the role of the microbiome. It has been demonstrated that the microbiome plays a key role in the metabolism, and in the efficacy and toxicity of pharmacological agents. Given its capacity to modulate many of the host processes, including the metabolism, inflammation and immune and cellular responses, it can potentially influence the response to or toxicity to treatment, and may even be key in cancer development. To this effect, the microbiome is a hugely interesting area of study that requires a new approach and intense collaboration between different disciplines, given that biological samples of faeces and saliva need to be obtained and patient participation is required to fill out questionnaires about diet and lifestyle throughout the course of their treatment.