ReviewDetection of single cell heterogeneity in cancer

Single cell heterogeneity has already been highlighted in cancer classification, diagnosis, and treatment. Recent advanced technologies have gained more ability to reveal the heterogeneity on single cell level. In this review, we listed various detection targets applied in single cell study, including tumor tissue cells, circulating tumor cells (CTCs), disseminated tumor cells (DTCs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), and cancer stem cells (CSCs). We further discussed and compared detection methods using these detection targets in different fields to reveal single cell heterogeneity in cancer. We focused not only on the methods that have already been established and validated, but also on newly developed methods. In morphology and phenotype, the methods mainly included cell imaging and immune-staining. In genomics and proteomics, the main methods were single cell sequencing and single cell western blotting. Collectively, from using these methods, we can have a better understanding of the single cell variation, as well as what kind of variation it is and how the variation works. Our observations imply that study on single cell heterogeneity in cancer is an important step to precision medicine. The development of technologies in detection of single cell heterogeneity will be sure to improve the diagnosis and treatment in cancer.