Does a tissue-specific Hox code underlie tumour organotropism?

People in parts of Wales, and especially North Wales, are diagnosed with cancer more often than the UK average, and many residents are older, which raises risk further. A key reason cancer is hard to cure is metastasis, where tumour cells spread to new organs. Curiously, they don’t spread everywhere: some organs offer more 'friendly soil' to cancer 'seeds' and others resist them. But why? We will test a new explanation for this phenomenon centred on Hox genes. These are master genetic switches that help set the identity of each tissue in the body, by turning other genes on and off. Different tissues (and different cancers) show their own 'Hox code'.

We propose that metastasis happens more readily when a tumour’s 'Hox code' is compatible with that of a target organ.

Using existing patient sequencing data, we will map 'Hox codes' in primary tumours, normal tissues, and matched metastases. We will look for patterns that predict which organs are most at risk. If successful, our work could enable earlier risk prediction, and point to new treatments that disrupt this tumour–organ compatibility, helping prevent secondary cancers and improving outcomes for people in Wales.