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.

中文翻译：

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人类癌症中的异常滋养层分化：一个新兴的新型治疗靶点（综述）。

各种类型的人类癌症可能会出现异常的滋养层分化，包括组织学变化和 β-人绒毛膜促性腺激素 (β-hCG) 表达的改变。上皮癌中滋养细胞分化异常通常与分化不良、肿瘤转移、不良预后和治疗耐药有关。由于 β-hCG 靶向疫苗在早期 II 期试验中失败，因此更好地了解人类癌症滋养细胞分化的分子发病机制至关重要。本综述总结了该主题的临床和转化研究，旨在加速有效靶向治疗的开发。β-hCG 的异位表达在体外可促进增殖、迁移、侵袭、血管生成和上皮间质转化 (EMT) ，并在体内增强转移和致瘤能力。β-hCG 调节的信号级联包括 TGF-β 受体途径、EMT 相关途径、c-MET 受体酪氨酸激酶和丝裂原激活蛋白激酶/ERK 途径以及 SMAD2/4 途径。总而言之，这些发现表明 TGF-β 受体、c-MET 和 ERK1/2 是潜在的治疗靶点。然而，为了改进这种侵袭性人类癌症的精准治疗设计，必须对异常滋养层分化的分子基础进行进一步研究。