Tumor heterogeneity is a major hindrance in cancer classification, diagnosis and treatment. Recent technological advances have begun to reveal the true extent of its heterogeneity. Single-cell analysis (SCA) is emerging as an important approach to detect variations in morphology, genetic or proteomic expression. In this review, we revisit the issue of inter-and intra-tumor heterogeneity, and list various modes of SCA techniques (cell-based, nucleic acid-based, protein-based, metabolite-based and lipidbased) presently used for cancer characterization. We further discuss the advantages of SCA over pooled cell analysis, as well as the limitations of conventional techniques. Emerging trends, such as high-throughput sequencing, are also mentioned as improved means for cancer profiling. Collectively, these applications have the potential for breakthroughs in cancer treatment.
Tumor Heterogeneity and EvolutionThe tumor microenvironment is a complex heterogeneous system and consists of intricate interactions between the tumor cells and its neighboring non-cancerous stromal cells. The principal stromal cells in the tumor niche consist of endothelial cells, macrophages, immune cells, fibroblasts and stem cells. Each cell has unique behaviors due to variation in genetic and environmental factors, which has implications in pathogenic conditions. 1 In cancer, nonrecurring mutations and large genomic alterations generate vast heterogeneity, giving rise to tumors which comprised subpopulations of distinct cells. Other factors, including clonal evolution and positive selective pressure from therapeutics, 2 also play a role in inducing tumor heterogeneity.Unlike prior literatures on cancer heterogeneity, 3,4 this review aims to evaluate and combine the issues of cancer heterogeneity with single-cell analysis (SCA), 5 summarizing the recent advances in single-cell cancer analysis which has allowed new understanding of cancer biology. These singlecell analytical techniques are classified into four different categories, including cell-based, nucleic acid-based, proteinbased and metabolite-based methods and are explicitly discussed along with the advantages and limitations for each technology. Finally, the review highlighted the importance of SCA techniques over bulk tissue analyses, and summarized the application of next generation omics to single cells. The objective of this review is to familiarize the reader with the burgeoning field of SCA in oncology, thereby empowering them to select the best approach for their specific application.
Different characteristics of single cellsCells work as single units or in organized tissues and organs. Despite the apparent synchrony in cellular systems, each cell