title: Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications.
abstract: Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.
authors.affiliation: Translational Cancer Therapeutics Lab, UCL Cancer Institute, University College London, London WC1E 6DD, UK.
authors.forename: Elza C
authors.initials: EC
authors.lastname: de Bruin
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading, Berkshire RG6 6AH, UK.
authors.forename: Tiffany B
authors.initials: TB
authors.lastname: Taylor
authors.affiliation: Translational Cancer Therapeutics Lab, UCL Cancer Institute, University College London, London WC1E 6DD, UK ; Translational Cancer Therapeutics Lab, Cancer Research UK London Research Institute, London WC2A 3LY, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton