Dormant and activated polyploid giant cancer cells: From chemoradiotherapy resistance to cancer progression.

Polyploid giant cancer cells (PGCCs) exhibit genomic instability and possess distinct biological features, contributing critically to cancer progression and therapeutic resistance. PGCCs are formed by endoreplication or cell fusion and generate daughter cells through asymmetric division. They can enter a dormant state through mechanisms involving, autophagy and dysfunctional P53, while acquiring therapeutic resistance via metabolic adaptations, angiogenesis, and DNA damage repair. The reactivation of PGCCs is influenced by inflammatory cues and the tumor microenvironment (TME). Once activated, both PGCCs and their daughter cells demonstrate robust invasive and migratory capacities, and collaborate with angiogenesis, epithelial-mesenchymal transition, and TME to drive cancer progression. PGCCs contribute to malignant metastasis and recurrence through dynamic interconversion between dormant and active states. Further elucidating the molecular mechanisms and factors that regulate PGCC dormancy and activation may provide therapeutic targets to overcome drug resistance and prevent tumor recurrence.