The role of oncogene-induced senescence in intestinal tumorigenesis

Colorectal tumours contain a dynamic mix of stem cells driven by mutations in the RAS and MYC pathways, and a new project will investigate whether these mutations push cells into a senescent state—a kind of suspended animation that can either suppress tumours or, paradoxically, help them grow. The problem is that scientists do not yet understand how oncogene-induced senescence (OIS) works in the gut. In the liver, low levels of OIS promote tumour formation while high levels protect the host. Whether the same spectrum exists in colorectal cancer, and how non-RAS mutations influence it, is unknown. This project will map the range of senescent states across human colorectal precursor lesions and cancers, and identify the specific driver mutations behind each state. This is fundamental science. If successful, it could reshape how researchers think about early tumour development in the bowel. A clearer picture of when senescence helps or harms might eventually inform strategies to tip the balance toward protection—but that is years away. For now, the work fills a basic gap in understanding how common cancer mutations actually behave inside living tissue.