title: Biological and therapeutic impact of intratumor heterogeneity in cancer evolution.
abstract: Precision medicine requires an understanding of cancer genes and mutational processes, as well as an appreciation of the extent to which these are found heterogeneously in cancer cells during tumor evolution. Here, we explore the processes shaping the cancer genome, placing these within the context of tumor evolution and their impact on intratumor heterogeneity and drug development. We review evidence for constraints and contingencies to tumor evolution and highlight the clinical implications of diversity within tumors. We outline the limitations of genome-driven targeted therapies and explore future strategies, including immune and adaptive approaches, to address this therapeutic challenge.
authors.affiliation: Cancer Research UK London Research Institute, London WC2A 3LY, UK; Centre for Mathematics & Physics in the Life Science & Experimental Biology (CoMPLEX), University College London, London WC1E 6BT, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: McGranahan
authors.affiliation: Cancer Research UK London Research Institute, London WC2A 3LY, UK; UCL Cancer Institute, Paul O'Gorman Building, Huntley Street, London WC1E 6DD, UK. Electronic address: charles.swanton@cancer.org.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D019143:Evolution, Molecular; D052138:Genes, Neoplasm; D018740:Genetic Heterogeneity; D023281:Genomics; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*