Plasticity in human gut & cancer

Although many resources are devoted to understanding and combating metastatic disease, it is striking how poorly we understand the timing and mechanisms by which metastatic competence first arises during tumour progression. Indeed, metastasis formation is classically considered to be a late-stage event in colorectal cancer evolution. However, a small fraction of these CRC patients are already at high risk to develop life threatening distant metastases immediately succeeding malignant transformation.

I will discuss our latest efforts where we pivoted our research focus towards understanding the earliest stages of CRC formation, that have long been considered inaccessible in patients, as they often go unnoticed. Using single-cell spatial atlases and functional organoid models from tumor regions before and after malignant transformation, the Snippert lab aims to capture ‘primordial signals’ that trigger metastatic competence – long before they are buried under thousands of genomic scars, fibrosis and inflammatory chaos known to late-stage cancers.