Unmasking tumor heterogeneity and clonal evolution by single-cell analysis

Abstract

The intratumoral heterogeneity orchestrated by the tumor intrinsic and extrinsic mechanisms enable cancers to persist and spread notwithstanding the use of aggressive interventional therapies. The heterogeneity is revealed at multiple levels - at the level of individual tumor cells, in the cellular composition of tumor infiltrates and in the chemical microenvironment in which the cells reside. Deconvoluting the complex nature of the cell types present in the tumor, along with the homo and heterotypic interactions between different cell types can produce novel insights of biological and clinical relevance. However, most techniques analyze tumors at a gross level missing key inter-cell-type genotypic and phenotypic differences. The advent of single-cell sequencing has given an unprecedented opportunity to analyze the tumor at a resolution that not only captures the diversity of the cellular composition of a tumor but also provides information on the genetic, epigenetic and functional states of different cell types. In this review, we summarize the genesis of tumor heterogeneity, its impact on tumor growth and progression and their clinical consequences. We present an overview of the currently available platforms for isolation and sequencing of single tumor cells and provide evidence of its utility in precision medicine and personalized therapy.

Keywords

Intratumoral heterogeneity / single-cell sequencing / clonal evolution / circulating tumor cells / drug resistance

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