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April 3, 2026Clinical and Molecular HepatologyOpen Access

Co-repression of Yap1 and Sox9 Abrogates Established Cholangiocarcinoma by Eliminating Transcriptional Compensation

Minwook Kim Song Hu Yoojeong Park Joseph Kwon Laura Molina Li-Ju Wang Jia-Jun Liu Silvia Liu Aatur Singhi Yu‐Chiao Chiu Sungjin Ko

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Key Points

This research aims to explore the effectiveness of co-targeting YAP1 and SOX9 in treating intrahepatic cholangiocarcinoma (iCCA) and overcoming therapeutic resistance.
Utilized a co-targeting approach to inhibit YAP1 and SOX9.
Investigated transcriptional compensation mechanisms in iCCA.
Analyzed the potential effects of combined inhibition on therapy effectiveness.
Co-targeting YAP1 and SOX9 significantly reduced tumor growth in iCCA models.
Adaptive resistance mechanisms to YAP1 inhibition were identified and may occur in other cancer types.
Findings suggest new therapeutic strategies for advanced YAP1-TEAD resistance cases.

Implication

Co-targeting SOX9 and YAP1 enhances treatment outcomes in cholangiocarcinoma, suggesting a broader application for resistant malignancies.

Abstract

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Cite This Study

Kim et al. (2026) studied this question.

synapsesocial.com/papers/69d1fe18a79560c99a0a48ca https://doi.org/10.3350/cmh.2025.1170

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Keep reading

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

1Co-expression of YAP and TAZ associates with chromosomal instability in human cholangiocarcinomaPrognostic Study · 2021 · 42 citations
2YAP inhibits autophagy and promotes progression of colorectal cancer via upregulating Bcl-2 expressionOriginal Research · 2021 · 128 citations
3<scp>YAP</scp>‐<scp>TEAD</scp> inhibition is associated with upregulation of an androgen receptor mediated transcription program providing therapeutic escape2024 · 7 citations
4YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factorsOriginal Research · 2015 · 233 citations
5Extracellular matrix reprogramming by the YAP/TAZ– TGF-ß2 axis drives immune exclusion in cholangiocarcinoma modelsOriginal Research · 2026 · 1 citations

Dual targeting of YAP1 and β-catenin: a therapeutic strategy for colorectal cancer2026
Unbalanced YAP–SOX9 circuit drives stemness and malignant progression in esophageal squamous cell carcinoma2018
Therapeutic potential of SOX9 dysruption in Combined Hepatocellular Carcinoma-Cholangiocarcinoma2024
GLP-1 receptor agonists and adverse outcomes in patients with type 2 diabetes and chronic viral hepatitisClinical and Molecular Hepatology · 2026
O-GlcNAcylation of GSDMD promotes mitochondrial dysfunction and hepatocyte injury in MASLDClinical and Molecular Hepatology · 2026

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