What is the research about?
Intra-tumoral heterogeneity (ITH) is the feature that explains the discrepancy between initial treatment response and subsequent tumor recurrence or metastasis associated with primary and acquired therapy resistance in human cancer. ITH is the net result of a highly dynamic evolutionary process and mediated by: (i) intrinsic programs (e.g. genetic and epigenetic alterations in malignant cells); (ii) extrinsic factors (e.g. signals from the microenvironment); and (iii) therapy-induced selection pressure (e.g. by drug treatment or radiation). To date, (epi)genomic and transcriptomic approaches have largely focused on characterizing the primary tumor in bulk, revealing aggregate cellular profiles camouflaging important aspects of ITH. The recent advent of single-cell "omics" profiling technologies paves the way for a revolution in our ability to comprehensively characterize ITH.