Pancreatic cancer EMT‑targeted therapy: Molecular mechanisms and clinical translation (Review)

作者：Guirui Zhang, Yongmo Wu, Mei‐Lin Wei, Shupeng Huang, Qinghao Wang, Zhengyi Xie, Sisi Liu, Jin Wang · 发表于：International Journal of Oncology · 年份：2026 · DOI：10.3892/ijo.2026.5867 · 被引用次数：4 · 研究领域：Cancer Cells and Metastasis、Pancreatic and Hepatic Oncology Research、Cancer, Stress, Anesthesia, and Immune Response

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a dismal 5‑year survival rate of ~9%, primarily due to late diagnosis, aggressive metastasis and profound resistance to conventional therapies. Epithelial‑mesenchymal transition (EMT) has been identified as a pivotal driver of these malignant phenotypes, facilitating early invasion, dissemination and treatment failure. The present review systematically elaborated on the multidimensional mechanisms underlying EMT in PDAC, emphasizing its operation as a spectrum of hybrid epithelial/mesenchymal states rather than a binary switch. Key molecular mechanisms include the activation of core transcription factors (such as Snail, ZEB, Twist), intricate crosstalk within the tumor microenvironment (such as transforming growth factor-β and hepatocyte growth factor signaling from stromal cells) and dynamic epigenetic reprogramming. Furthermore, EMT critically contributes to the acquisition of cancer stem cell properties and enhances the survival and colonization of circulating tumor cells. The present review also outlined emerging translational strategies targeting EMT‑related pathways, highlighting agents such as STNM01 that have entered early-phase clinical trials. By synthesizing unprecedented insights into EMT's plastic spectrum states and subtype‑specific regulatory networks, this work establishes a paradigm‑shifting framework for advancing EMT‑targeted therapies; offering transformative potentia...