Modelling the monstrosities: experimental and computational systems for studying polyploid giant cancer cells

Area of Science:

• Oncology
• Cancer Biology
• Translational Research

Background:

• Polyploid Giant Cancer Cells (PGCCs) are a tumor subpopulation implicated in metastasis, recurrence, and therapy resistance.
• Inconsistent model systems and lack of standardization impede mechanistic understanding and clinical application of PGCC research.

Purpose of the Study:

• To methodically analyze various model systems used in Polyploid Giant Cancer Cell (PGCC) research.
• To highlight pluralistic research efforts for the clinical application of PGCC findings.
• To fill the existing gap in the literature regarding standardized PGCC model systems.

Main Methods:

• A systematic literature review of scholarly articles published up to November 2025.
• Databases searched include Google Scholar, PubMed, and ScienceDirect.
• Focus on literature examining PGCC development, characteristics, and functional roles in cancer.

Main Results:

• In vitro models offer mechanistic insights and drug screening but lack physiological relevance.
• Ex vivo tumor explants and organoids retain patient-specific traits and hold translational potential.
• In vivo models (e.g., Drosophila, mouse xenografts) reveal PGCC functions in complex tissue environments.
• No single model system fully recapitulates PGCC biology, indicating a need for integrated, multi-model strategies.
• Integrating patient-derived organoids with lineage-traced xenografts and single-cell omics allows continuous tracking of PGCC development and diversity.

Conclusions:

• The development of PGCC-targeted therapies is currently lacking.
• Advancements in model systems, single-cell analysis, and imaging capabilities are crucial for therapeutic progress.
• Continued model development is essential for translating PGCC biology into predictive diagnostics and effective treatments.