Application of single-cell sequencing in human cancer

Abstract

Precision medicine is emerging as a cornerstone of future cancer care with the objective of providing targeted therapies based on the molecular phenotype of each individual patient. Traditional bulk-level molecular phenotyping of tumours leads to significant information loss, as the molecular profile represents an average phenotype over large numbers of cells, while cancer is a disease with inherent intra-tumour heterogeneity at the cellular level caused by several factors, including clonal evolution, tissue hierarchies, rare cells and dynamic cell states. Single-cell sequencing provides means to characterize heterogeneity in a large population of cells and opens up opportunity to determine key molecular properties that influence clinical outcomes, including prognosis and probability of treatment response. Single-cell sequencing methods are now reliable enough to be used in many research laboratories, and we are starting to see applications of these technologies for characterization of human primary cancer cells. In this review, we provide an overview of studies that have applied single-cell sequencing to characterize human cancers at the single-cell level, and we discuss some of the current challenges in the field.

Figure 1.

The role of single-cell molecular phenotyping in characterization of tumour heterogeneity and in clinical applications. Multiple molecular mechanisms and environmental factors lead to intra-tumour heterogeneity. Single-cell molecular phenotyping enables characterization of many aspects of intra-tumour heterogeneity and has the potential to be applied to generate clinically relevant information.

Figure 2.

Overview of the process of applying single-cell sequencing to patient-derived tumour samples.