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Transient YAP/TAZ inhibition exposes therapeutic vulnerabilities in advanced cancers [RNA-Seq]

GSE301491 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2026/06/17 Platform GPL19057
Summary
YAP and TAZ, key effectors of the Hippo pathway, are frequently hyperactivated in cancer, where they drive tumor progression and resistance to therapy. Their oncogenic activity relies on interaction with TEAD transcription factors, making the TEAD-YAP/TAZ complex an attractive therapeutic target. Using translational mouse models, we demonstrate that sustained systemic YAP/TAZ depletion leads to severe side effects. However, even transient YAP/TAZ inhibition alone is sufficient to suppress tumor growth in advanced stages. Mechanistically, YAP/TAZ activity promotes T cell exclusion from the tumors by inducing target genes involved tissue remodelling. Consequentially, YAP/TAZ inhibition induces immune infiltration, but the infiltrating T cells rapidly become exhausted. Combining YAP/TAZ inhibition with immune checkpoint blockade (ICB) overcomes this exhaustion and sensitizes previously resistant tumors to immunotherapy.
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Direct links to NCBI, no account and no request form: the whole study as GSE301491_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1285342 and SRA study SRP597412. Searching any of these in the dataset finder brings you back here.

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