Cell plasticity and genomic instability in cancer evolution

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.

Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells

“…Such plasticity, or heterogeneity, is the lifeline for cancer cells, as it helps cancer cells to survive and become dominant under multiple levels of constraints. Constant change is the winning strategy for cancer cells, and genome instability is a powerful mechanism that allows both the survival (by changing genome structure within the macroevolutionary phase) and fitness (by changing gene mutation/epigenetic profile within the microevolutionary phase) of cancer cells [11][12][13][14]. Genomic instability can give rise to gene mutations, chromosomal translocations, alternations of copy number, deletions, and inversions of pieces of DNA [15].…”

Hallmarks of cancer resistance

“… 11 Genomic instability is a phenomenon that can cause DNA damage and activate DNA damage response (DDR) signaling pathways. 12 It can be induced by various factors such as exposure to radiation, chemicals, and other environmental stressors. 12 Genomic instability can lead to genetic alterations such as mutations, chromosomal rearrangements, and copy number variations, which can contribute to the development of cancer ( Figure 1 ).…”

“… 12 It can be induced by various factors such as exposure to radiation, chemicals, and other environmental stressors. 12 Genomic instability can lead to genetic alterations such as mutations, chromosomal rearrangements, and copy number variations, which can contribute to the development of cancer ( Figure 1 ). 13 In addition to its role in cancer initiation, genomic instability can also play a role in cancer resistance to therapy.…”