Aberrant trophoblastic differentiation in human cancer: An emerging novel therapeutic target (Review)

Chang,Chen; Chen,Yi-Lin; Wang,Yi-Wen; Chen,Hui-Wen; Hsu,Che-Wei; Lin,Kun-Che; Ou,Yin-Chien; Liu,Tsunglin; Chen,Wan-Li; Chu,Chien-An; Ho,Chung-Liang; Lee,Chung-Ta; Chow,Nan-Haw

doi:10.3892/or.2024.8701

Aberrant trophoblastic differentiation in human cancer: An emerging novel therapeutic target (Review)

Authors:
- Chen Chang
- Yi-Lin Chen
- Yi-Wen Wang
- Hui-Wen Chen
- Che-Wei Hsu
- Kun-Che Lin
- Yin-Chien Ou
- Tsunglin Liu
- Wan-Li Chen
- Chien-An Chu
- Chung-Liang Ho
- Chung-Ta Lee
- Nan-Haw Chow
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Affiliations: Department of Pathology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, R.O.C., Department of Pathology, National Cheng Kung University Hospital, Tainan 704, Taiwan, R.O.C., Department of Dental Technology, Shu‑Zen Junior College of Medicine and Management, Kaohsiung 821, Taiwan, R.O.C., Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan, R.O.C., The Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan 701, Taiwan, R.O.C.
Published online on: January 15, 2024 https://doi.org/10.3892/or.2024.8701
Article Number: 43
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of β‑human chorionic gonadotropin (β‑hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentiation, tumor metastasis, unfavorable prognosis and treatment resistance. Since β‑hCG‑targeting vaccines have failed in an early phase II trial, it is crucial to obtain a better understanding of the molecular pathogenesis of trophoblastic differentiation in human cancer. The present review summarizes the clinical and translational research on this topic with the aim of accelerating the development of an effective targeted therapy. Ectopic expression of β‑hCG promotes proliferation, migration, invasion, vasculogenesis and epithelial‑mesenchymal transition (EMT) in vitro, and enhances metastatic and tumorigenic capabilities in vivo. Signaling cascades modulated by β‑hCG include the TGF‑β receptor pathway, EMT‑related pathways, the c‑MET receptor tyrosine kinase and mitogen‑activated protein kinase/ERK pathways, and the SMAD2/4 pathway. Taken together, these findings indicated that TGF‑β receptors, c‑MET and ERK1/2 are potential therapeutic targets. Nevertheless, further investigation on the molecular basis of aberrant trophoblastic differentiation is mandatory to improve the design of precision therapy for this aggressive type of human cancer.

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