title: Adapting clinical paradigms to the challenges of cancer clonal evolution.
abstract: Emerging evidence suggests that cancer branched evolution may affect biomarker validation, clinical outcome, and emergence of drug resistance. The changing spatial and temporal nature of cancer subclonal architecture during the disease course suggests the need for longitudinal prospective studies of cancer evolution and robust and clinically implementable pathologic definitions of intratumor heterogeneity, genetic diversity, and chromosomal instability. Furthermore, subclonal heterogeneous events in tumors may evade detection through conventional biomarker strategies and influence clinical outcome. Minimally invasive methods for the study of cancer evolution and new approaches to clinical study design, incorporating understanding of the dynamics of tumor clonal architectures through treatment and during acquisition of drug resistance, have been suggested as important areas for development. Coordinated efforts will be required by the scientific and clinical trial communities to adapt to the challenges of detecting infrequently occurring somatic events that may influence clinical outcome and to understand the dynamics of cancer evolution and the waxing and waning of tumor subclones over time in advanced metastatic epithelial malignancies.
authors.affiliation: University College London Cancer Institute, London, United Kingdom.
authors.forename: Nirupa
authors.initials: N
authors.lastname: Murugaesu
authors.forename: Su Kit
authors.initials: SK
authors.lastname: Chew
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D060965:Clonal Evolution; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D014411:Neoplastic Stem Cells / Q000473:pathology; D010802:Phylogeny; D012107:Research Design; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor