title: Implications of intratumour heterogeneity for treatment stratification.
abstract: Despite advances in the diagnosis and treatment of cancer, the majority of advanced metastatic solid tumours remain incurable. Differential gene expression, somatic mutational status, tumour-specific genetic signatures and micro-environmental selection pressures within individual tumours have implications for the success of predictive assays to guide therapeutic intervention. In this review we discuss the evidence for genetic and phenotypic heterogeneity and its potential implications for clinical decision making. We highlight areas of research that could be improved in order to better stratify patient treatment. We also discuss the predictive potential of patient-derived models of tumour response, including xenograft and cell line-based systems within the context of intratumour heterogeneity.
authors.affiliation: Translational Cancer Therapeutics Laboratory, Cancer Research UK London Research Institute, London, WC2A 3LY, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Crockford
authors.forename: Mariam
authors.initials: M
authors.lastname: Jamal-Hanjani
authors.forename: James
authors.initials: J
authors.lastname: Hicks
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D023281:Genomics / Q000379:methods; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: intratumour heterogeneity; patient-derived xenograft models; personalized medicine