Cell plasticity and genomic instability in cancer evolution
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REVIEW ARTICLE
Cell plasticity and genomic instability in cancer evolution Yan Xu1 · Hui Li1,2 · Fan Yang1 · Dingpeng Yang1 · Bin‑Bing S. Zhou1,2 Received: 30 May 2020 / Revised: 26 August 2020 / Accepted: 15 September 2020 © Shenzhen University School of Medicine; Fondazione Istituto FIRC di Oncologia Molecolare 2020
Abstract Cancer cells evolve throughout disease progression and tumor relapse. Such evolution is a dynamic process resulting in genotypic and phenotypic cellular changes, conferring a high level of cell plasticity. Data derived from next-generation sequencing strategies have implicated that cancer cell plasticity could be driven by genetic changes induced by genomic instability during cancer evolution. Understanding the mechanisms of how genomic instability promotes mutagenesis and cancer cell plasticity could thus be critical avenue for cancer prevention and intervention. In this review, we discuss the relationships between cancer cell plasticity, genomic instability and mutagenesis during cancer evolution. We offer our insight and opinion on therapeutic strategies in this rapidly progressing research field. Keywords Oncogene · Tumor suppressor · Cell plasticity · Genomic instability · Cancer evolution
Introduction Cancer derives from aberrantly proliferating cells that can avoid cell death and persist despite an accumulation of genetic mutations. After initial malignant transformation, cancer cells continue to evolve during disease progression and tumor relapse (Alexandrov et al. 2020; Lipinski et al. 2016). As a committed champion of evolutionism, Dr. Peter Nowell proposed the cancer clonal evolution theory, whereby cancer clones with a survival advantage can prevail under selection pressure (Nowell 1976). Similar to the classical species evolution model, cancer evolution is a dynamic process: various genotypic and phenotypic cellular changes can occur to confer a high degree of cell plasticity (Boumahdi and de Sauvage 2020; Yuan et al. 2019). As a main inducer of cancer heterogeneity and drug resistance, cell plasticity is driven by diverse causes, such as exogenous
selection pressures (including environmental and treatment stress) and endogenous adaptability (including genetic and epigenetic instability) (Boumahdi and de Sauvage 2020; Yuan et al. 2019). Both oncogenes and tumor suppressors can affect cellular plasticity and adaptability. Data derived from next-generation sequencing approaches have implicated that cancer cell plasticity could be driven by numerous genetic changes during cancer evolution (Alexandrov et al. 2020; Ferrando and Lopez-Otin 2017) and revealed significant intra-tumoral heterogeneity in cancer cells. What’s more, genomic instability seems to not only change cellular phenotypes, but also alter cancer cell adaptability and plasticity in response to environmental changes and treatment pressures. In this review, we highlight the emerging connection between cancer cell plasticity, genomic instability and mutagenesis during cancer evolution, and offer our insight and opini
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