ArticleEMBO reports2024
Identification of resistance mechanisms to small-molecule inhibition of TEAD-regulated transcription.
Article in EMBO reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed.
- Hippo-YAP/TAZ Signaling in Astrocytes and Microglia: Role in Neuroinflammation, Neurodegeneration and Glial Tumors.International journal of molecular sciences · 2026Review
- Comprehensive analysis of TEAD inhibition in meningioma identifies MEK and mTOR inhibition as effective combination therapies against resistant lines.bioRxiv : the preprint server for biology · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Targeting the Hippo pathway in cancer.Nature reviews. Drug discovery · 2025Review
- TEAD-targeting small molecules induce a cofactor switch to regulate the Hippo pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Epithelioid Hemangioendothelioma: Treatment Landscape and Innovations for an Ultra-Rare Sarcoma.Current treatment options in oncology · 2025Review
- ZDHHC14-Mediated TEAD4 Palmitoylation Drives Th17 Cell Recruitment in Renal Immunopathology.Research (Washington, D.C.) · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
The Hippo tumor suppressor pathway controls transcription by regulating nuclear abundance of YAP and TAZ, which activate transcription with the TEAD1-TEAD4 DNA-binding proteins. Recently, several small-molecule inhibitors of YAP and TEADs have been reported, with some entering clinical trials for different cancers with Hippo pathway deregulation, most notably, mesothelioma. Using genome-wide CRISPR/Cas9 screens we reveal that mutations in genes from the Hippo, MAPK, and JAK-STAT signaling pathways all modulate the response of mesothelioma cell lines to TEAD palmitoylation inhibitors. By exploring gene expression programs of mutant cells, we find that MAPK pathway hyperactivation confers resistance to TEAD inhibition by reinstating expression of a subset of YAP/TAZ target genes. Consistent with this, combined inhibition of TEAD and the MAPK kinase MEK, synergistically blocks proliferation of multiple mesothelioma and lung cancer cell lines and more potently reduces the growth of patient-derived lung cancer xenografts in vivo. Collectively, we reveal mechanisms by which cells can overcome small-molecule inhibition of TEAD palmitoylation and potential strategies to enhance the anti-tumor activity of emerging Hippo pathway targeted therapies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.