Detecting repeated cancer evolution in human tumours from multi-region sequencing data

The biggest clinical challenge in oncology is the fact the tumours change over time, progressing from benign to malignant, becoming metastatic, and developing treatment resistance1,2. This occurs through a process of clonal evolution involving cancer cells and their microenvironment3. Intra-tumour heterogeneity (ITH), or the genetic and phenotypic variation of cancer cells within the same tumour, is the natural consequence of this evolutionary process. ITH is also a key factor contributing to the lethal outcome of cancer, as it provides the substrate of phenotypic variation upon which adaptation can occur4. A fundamental question in oncology is therefore: can we predict a cancer's next evolutionary "step"?