Applications of high-resolution clone tracking technologies in cancer

Tumors are comprised of dynamic, heterogenous cell populations characterized by numerous genetic and non-genetic alterations that accumulate and change with disease progression and treatment. Retrospective analyses of tumor evolution have relied on the measurement of genetic markers (such as copy number variants) to infer clonal dynamics. However, these approaches neglect the critical contributions of non-genetic drivers of disease. Techniques that harness the power of prospective clone tracking via heritable barcode tags provide an alternative strategy. In this review, we discuss methods for high-resolution, quantitative clone tracking, including recent advancements to pair barcode-specific functionality with scRNA-seq, clonal cell isolation, and in situ hybridization and imaging. We discuss these approaches in the context of cancer cell heterogeneity and treatment resistance.