Polyploid giant cancer cells: Underlying mechanisms, signaling pathways, and therapeutic strategies

Polyploid giant cancer cells (PGCCs) are characterized by enlarged nuclei, association with tumors, and resistance to treatment, contributing significantly to cellular heterogeneity. These cells arise from endoreplication and cell fusion, often triggered by stressors such as radiation and chemotherapy. PGCCs exhibit chromosomal instability and aneuploidy, leading to poor prognosis in various cancers. Key features include the ability to produce progeny cells via amitotic division and the expression of cancer stem cell markers. PGCC formation and function involve signaling pathways like cell fusion (GCM1/syncytin-1), cell cycle control, stress response, and EMT. Understanding these pathways is crucial for identifying therapeutic targets. Current therapeutic strategies targeting PGCCs involve drugs like azacitidine, decitabine, and zoledronic acid, as well as DNMT inhibitors in combination therapies. These approaches aim to reverse drug resistance and enhance antitumor efficacy. Furthermore, microRNAs (miRNAs) are pivotal in regulating gene expression and influencing the cell cycle, proliferation, and apoptosis. Cataloging miRNAs and understanding their function is critical for developing potential cancer treatments. Researchers are exploring miRNA-based modulation of signaling pathways to block tumor growth. This review highlights the complex biology of PGCCs and emphasizes the need for targeted therapies to improve cancer treatment outcomes.