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

Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of beta-human chorionic gonadotropin (beta-hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentiation, tumor metastasis, unfavorable prognosis and treatment resistance. Since beta-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 beta-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 beta-hCG include the TGF-beta 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-beta 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.