The life cycle of polyploid giant cancer cells and dormancy in cancer: Opportunities for novel therapeutic interventions

Abstract Recent data suggest that most genotoxic agents in cancer therapy can lead to shock of genome and increase in cell size, which leads whole genome duplication or multiplication, formation of polyploid giant cancer cells, activation of an early embryonic program, and dedifferentiation of somatic cells. This process is achieved via the giant cell life cycle, a recently proposed mechanism for malignant transformation of somatic cells. Increase in both cell size and ploidy allows cells to completely or partially restructures the genome and develop into a blastocyst-like structure, similar to that observed in blastomere-stage embryogenesis. Although blastocyst-like structures with reprogrammed genome can generate resistant or metastatic daughter cells or benign cells of different lineages, they also acquired ability to undergo embryonic diapause, a reversible state of suspended embryonic development in which cells enter dormancy for survival in response to environmental stress. Therapeutic agents can activate this evolutionarily conserved developmental program, and when cells awaken from embryonic diapause, this leads to recurrence or metastasis. Understanding of the key mechanisms that regulate the different stages of the giant cell life cycle offers new opportunities for therapeutic intervention.