Genetic and non-genetic clonal diversity in cancer evolution

This Review discusses the role of functional (impacting tumour phenotype) and non-functional intra-tumour heterogeneity (ITH) in cancer evolution, highlighting the importance of considering genetic and non-genetic factors and their impact on patient outcomes. The observation and analysis of intra-tumour heterogeneity (ITH), particularly in genomic studies, has advanced our understanding of the evolutionary forces that shape cancer growth and development. However, only a subset of the variation observed in a single tumour will have an impact on cancer evolution, highlighting the need to distinguish between functional and non-functional ITH. Emerging studies highlight a role for the cancer epigenome, transcriptome and immune microenvironment in functional ITH. Here, we consider the importance of both genetic and non-genetic ITH and their role in tumour evolution, and present the rationale for a broad research focus beyond the cancer genome. Systems-biology analytical approaches will be necessary to outline the scale and importance of functional ITH. By allowing a deeper understanding of tumour evolution this will, in time, encourage development of novel therapies and improve outcomes for patients.

Automated summary

This article discusses the importance of functional and non-functional intra-tumour heterogeneity (ITH) in cancer evolution. It emphasizes the need to consider genetic and non-genetic factors in tumor evolution, and highlights the role of systems-biology analytical approaches in understanding the functional ITH. Ultimately, deepening our understanding of tumour evolution through functional ITH will lead to the development of novel therapies and improved outcomes for patients.