MET inhibition exploits conserved regulatory dependencies in malignant rhabdoid tumors

MET inhibition is a selective vulnerability in extrarenal malignant rhabdoid tumors, where HGF/MET signaling is linked to cytotoxicity and complete in vivo response.

• Why it matters: MRTs are lethal childhood cancers with universal SWI/SNF dysregulation, but the regulatory programs and actionable dependencies that sustain them are not well defined.
• What they did: The study integrated single-cell multi-omics and spatial transcriptomics across diverse MRTs to nominate dependencies, then functionally validated them in matched patient-derived models and performed a curated drug screen.
• The result: A conserved metaprogram centered on TCF12, ZNF148 and CHD2 supported niche-conditioned transcription, and MET expression in primary tumors correlated with response, enabling biomarker-guided stratification for clinical translation.

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