Aberrant Trophoblastic Differentiation in Human Cancer: An Emerging Novel Therapeutic Target (Review)

Overview

Journal Oncol Rep

Specialty Oncology

Date 2024 Jan 19

PMID 38240107

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

Affiliations

Soon will be listed here.

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) , and enhances metastatic and tumorigenic capabilities . 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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