Colorectal cancer (CRC) represents approximately 10% of all cancers and is the second leading cause of cancer-related deaths worldwide. Genomic-based precision medicine has raised hopes of improved cancer survival rates by tailoring the treatment to the specific molecular alterations underlying this and other cancers. However, in translational trials using large-scale genomic sequencing, personalised treatments were identified for less than 20% of patients. This limited success highlights the need to integrate the complex, dynamic and heterogeneous genotypes and phenotypes of the cancer ecosystem. This ecosystem includes the recently described microbiota-gene-drug interface, which now opens new opportunities to target CRC. Through 8 scientific and 2 central projects, implemented by a highly gender-balanced group of PIs (including 6 junior PIs) that bring together the required wide array of expertise, the GenoMiCC research unit will address functional genomics and microbiomics in CRC, in order to identify new druggable and accessible targets for personalised therapy. Together, our team of basic and clinician scientists will extend existing cooperations to transfer novel findings into next generation precision medicine-based clinical trials.
Colorectal cancer (CRC) remains a major global health burden, with high mortality and limited treatment options, particularly in advanced and metastatic stages. While genomics-driven precision medicine has offered some promise, its overall clinical success in CRC is limited due to low druggability of targets and poor understanding of the functional consequences of detected mutations. Functional precision oncology, using ex vivo patient-derived models such as organoids, has emerged as a promising complementary strategy, but challenges remain—particularly in modelling tumor heterogeneity, microenvironmental factors, and microbiome influences.
Recent advances highlight the critical role of the gut and intratumoral microbiota, as well as microbial metabolites, in modulating CRC progression, drug resistance, and therapy response. Studies have shown that these microbial ecosystems directly interact with cancer cells and host immunity, influencing metabolic pathways and potentially sensitizing tumors to therapies, including chemotherapy and immunotherapy.
This project brings together an interdisciplinary consortium of basic scientists and clinician-scientists to address three core aims: (1) characterizing microbiota–CRC interactions during disease progression and metastasis, (2) dissecting how CRC genomic alterations interact with microbial signals, and (3) understanding how microbiota and their metabolites influence therapy response and resistance. The ultimate goal is to uncover novel microbiota–drug–gene interaction networks and to develop new molecular and microbial co-targeting strategies for improved CRC treatment.
The GenoMiCC research unit will integrate cutting-edge functional models (e.g., PDOs, GEMMs, engineered microbiota), advanced single-cell and spatial profiling technologies, metabolomics, and computational biology. Central projects on microbiomics/metabolomics (CP1) and data management (CP2) will ensure harmonization and support for all scientific efforts. Internationally recognized collaborators contribute unique expertise in spatial microbiome analysis, gene regulation, and biomedical engineering.
Together, this initiative aims to create a sustainable research platform for translational cancer research and establish the foundation for next-generation precision oncology in CRC.