REVIEW article
Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1611920
This article is part of the Research TopicComparative Genomics and Functional Genomics Analyses in CancerView all 6 articles
Polyploid Giant Cancer Cells and Tumor Budding: Translation from Basic Research to Clinical Application
Provisionally accepted- 1School of Medicine, Nankai University, Tianjin, China
- 2Department of Scientific and Technology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
- 3College of Life Sciences, Nankai University, Tianjin, China
- 4Tianjin Union Medical Centre, Nankai University, Tianjin, China
- 5Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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Polyploid giant cancer cells (PGCCs) represent a distinct subpopulation of tumor cells characterized by enlarged or multiple nuclei and aneuploidy. PGCCs are products of genomic instability, possessing cancer stem cell properties and exhibiting significant resistance to radiotherapy and chemotherapy. They can generate highly invasive daughter cells through asymmetric division, exhibiting epithelial-mesenchymal transition characteristics, and facilitating tumor recurrence and metastasis. In vivo, PGCCs with daughter cells in tumor tissue can migrate and infiltrate into the forefront stroma to form tumor budding, which are closely related to solid tumor recurrence, metastasis, and drug resistance. Studies have shown that inhibiting sphingolipid enzyme acid ceramidase or regulating autophagy can reduce the production of PGCCs with daughter cells. Under appropriate induction conditions, PGCCs with daughter cells can be induced to differentiate into benign tissues such as adipocytes, chondrocytes, and osteocytes, inhibiting their malignant proliferation and invasive destruction. This study reviewed the recent research developments regarding PGCCs, mainly explored the endogenous mechanisms of PGCCs formation and their malignant phenotype, as well as the process of tumor budding formation in vivo and potential therapeutic strategies targeting PGCCs. The main novelty of this study lies in exploring the translation of PGCCs basic research into the clinical pathological prognostic role of tumor budding, which can reveal the potential mechanism of PGCCs/tumor budding formation at the molecular level, providing theoretical basis for prognosis assessment, monitoring of recurrence and metastasis risks, as well as 4 improving drug resistance and targeted therapy in cancer patients.
Keywords: tumor budding, metastasis, Drug Resistance, therapeutic strategies, Polyploid giant cancer cells (PGCCs)
Received: 15 Apr 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Huang, Wu, Yang, Li, Fei and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Fei Fei, Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
Yongjun Yu, Tianjin Union Medical Centre, Nankai University, Tianjin, 300071, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.