Over the last 2 years, there have been an unprecedented number of publications focused on cancer evolutionary processes in solid and haematological cancers, a trend that is set to continue over the next decade. In this editorial, insights and future perspectives of these studies as well as the research priorities for the Annals of Oncology Precision Medicine editorial board will be discussed. It is increasingly clear that many advanced tumours follow a branched, Darwinian evolutionary trajectory. This has been demonstrated in childhood ALL [1], pancreatic cancer [2, 3], colorectal cancer [4], clear cell renal carcinoma [5, 6], breast cancer [7, 8] and prostate cancer [9] among others. Next-generation sequencing studies have demonstrated that cancers share common clonal origins marked by early founder mutations and/ or DNA copy-number events. Sub-clones are defined by mutations that occur later in cancer evolution, occurring in some cells but not others. Following branched evolution, multiple sub-clones can co-exist, spatially separated within the same tumour or intermixed within the same biopsy. Importantly, the presence of sub-clones and the resulting intra-tumour heterogeneity is not synonymous with branched evolution; linear evolution with incomplete selective sweeps may still result in sub-clonal intermixing and intra-tumour heterogeneity.
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