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Beyond Cancer Stem Cells: Understanding Cancer Heterogeneity Through Gene Regulatory Networks and Single Cell Analysis

Ivan Gomez, Mitra Mojtahedi and Wei Wu

Cancer is a genetic and developmental disorder. The recent advents of systematic sequencing studies have revealed thousands of somatic mutations, hundreds of chromosome rearrangements and copy number variants in the cancer genomes. The genomic changes can differ markedly between individual cancers, even within a particular cancer type, individual tumours often display wide variations. Heterogeneity of cancer or cancer cells is the well observed phenomenon and is considered the major hurdle for successful treatment. Mutational clonal evolution and cancer stem cell models could only partially explain the ubiquitous heterogeneous tumour cell population. Here we provide intuitive thinking with systems biology view to explain the inevitable heterogeneity of cancer cells as an abnormal cell type driven by dynamics of gene regulatory network. We also discuss the significance of the single cell transcriptome for detecting the heterogeneous cancer cells and targeted therapy.