Cancer heterogeneity: implications for targeted therapeutics

Developments in genomic techniques have provided insight into the remarkable genetic complexity of malignant tumours. There is increasing evidence that solid tumours may comprise of subpopulations of cells with distinct genomic alterations within the same tumour, a phenomenon termed intra-tumour heterogeneity. Intra-tumour heterogeneity is likely to have implications for cancer therapeutics and biomarker discovery, particularly in the era of targeted treatment, and evidence for a relationship between intra-tumoural heterogeneity and clinical outcome is emerging. Our understanding of the processes that exacerbate intra-tumoural heterogeneity, both iatrogenic and tumour specific, is likely to increase with the development and more widespread implementation of advanced sequencing technologies, and adaptation of clinical trial design to include comprehensive tissue collection protocols. The current evidence for intra-tumour heterogeneity and its relevance to cancer therapeutics will be presented in this mini-review. Tumour heterogeneity refers to the existence of subpopulations of cells, with distinct genotypes and phenotypes that may harbour divergent biological behaviours, within a primary tumour and its metastases, or between tumours of the same histopathological subtype (intra- and inter-tumour, respectively). With the advent of deep sequencing techniques, the extent and prevalence of intra-and inter-tumour heterogeneity is increasingly acknowledged