Open Access

REVIEW

Multidimensional Regulatory Network of YAP1 Driving Malignant Progression in Esophageal Cancer: Molecular Mechanisms and Targeted Therapy: A Review

Jun-Hui Chen¹, Si-Run Du¹, Chang Liu¹, Bei-Bei Liu¹, Hai-Ying Xu², Xin-Ying Ji², Bo Feng³, Chun-Zheng Ma³, Jun-Hui Guo^3,*

1 The Second School of Clinical Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China
2 Henan Provincial Research Center of Engineering Technology for Nuclear Protein Medical Detection, Zhengzhou Health College, Zhengzhou, China
3 Department of Oncology, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China

* Corresponding Author: Jun-Hui Guo. Email:

(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research 2026, 34(5), 11 https://doi.org/10.32604/or.2026.073484

Received 19 September 2025; Accepted 20 January 2026; Issue published 22 April 2026

Abstract

Esophageal cancer (EC) ranks among the most lethal gastrointestinal malignancies. Due to challenges in early diagnosis, molecular heterogeneity, and therapeutic resistance, patient prognosis remains extremely poor, necessitating the development of novel biomarkers and therapeutic targets. As a core effector of the Hippo signaling pathway, the potential significance of Yes-associated protein 1 (YAP1) has garnered increasing attention. This paper aims to systematically summarize the multi-omics research, molecular mechanisms, and preclinical/translational evidence for YAP1, covering its activation pathways, biological functions, clinical significance, and therapeutic strategies. We elucidated YAP1’s multidimensional regulatory network in EC, including Hippo-dependent and -independent mechanisms, cross-regulation with environmental risk factors, and its role in malignant phenotypes such as cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and metastasis. The potential of YAP1 as a diagnostic, prognostic, and predictive biomarker is evaluated, alongside summarizing its role in mediating chemotherapy, radiotherapy, and immune tolerance mechanisms, along with recent advances in targeted therapies. This provides a theoretical foundation for subsequent basic research and precision medicine translation. As a potential hub in the EC signaling network, it is considered to play a key role in driving tumor progression and treatment resistance through multiple pathways. Targeting YAP1 holds broad clinical promise but faces challenges including functional duality, subtype heterogeneity, and complex resistance mechanisms. Future efforts should focus on developing highly selective inhibitors, integrating multi-omics technologies and innovative models to advance clinical translation and provide new strategies for precision treatment of EC patients.

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