Understanding Polyploid Giant Cancer Cells: From Molecular Mechanisms to Clinical Implications

Polyploid giant cancer cells (PGCCs) are characterized by abnormal enlargement and considerable polyploidy. Though the presence of giant cancer cells has been documented for decades, they remain not fully understood, especially in clinical practice, due to diagnostic challenges, and confusion regarding synonyms for PGCCs still exists. Thus, understanding PGCCs may be a key clue to overcoming them. This review offers a comprehensive overview of PGCCs, integrating insights from basic research and clinical studies to enhance understanding of their complex biology and clinical implications. In basic research, PGCCs are known to emerge under various stressors, including chemotherapy exposure, radiation, viral infection, and hypoxic environments. These cells play crucial roles in tumor progression through multiple mechanisms: enhancing genetic diversity, and facilitating metastatic spread via asymmetric cell division and genomic instability. In clinical studies, PGCC-containing tumors have been shown to exhibit marked treatment resistance and are associated with a poor prognosis across multiple solid tumor types, including prostate, lung, and pancreatic cancers. Despite these therapeutic challenges, paclitaxel-containing regimens have shown promising results in PGCC-containing tumors, such as pleomorphic carcinoma of the lung and undifferentiated carcinoma of the pancreas. Furthermore, emerging targeted therapies directed at specific pathways in PGCCs, particularly those involving TP53, represent potential strategies to improve clinical outcomes of patients with PGCC-containing tumors.