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

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

Research output: Contribution to journalReview articlepeer-review


Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of β‑human chorionic gonado‑ tropin (β‑hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentia‑ tion, 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 acceler‑ ating the development of an effective targeted therapy. Ectopic expression of β‑hCG promotes proliferation, migration, inva‑ sion, 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 recep‑ tors, 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.

Original languageEnglish
Article number43
JournalOncology Reports
Issue number3
Publication statusPublished - 2024 Mar

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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