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{
  "pmid": "39232581",
  "doi": "10.1016/j.ccell.2024.08.006",
  "abstract": "Diffuse hemispheric gliomas, H3G34R/V-mutant (DHG-H3G34), are lethal brain tumors lacking targeted therapies. They originate from interneuronal precursors; however, leveraging this origin for therapeutic insights remains unexplored. Here, we delineate a cellular hierarchy along the interneuron lineage development continuum, revealing that DHG-H3G34 mirror spatial patterns of progenitor streams surrounding interneuron nests, as seen during human brain development. Integrating these findings with genome-wide CRISPR-Cas9 screens identifies genes upregulated in interneuron lineage progenitors as major dependencies. Among these, CDK6 emerges as a targetable vulnerability: DHG-H3G34 tumor cells show enhanced sensitivity to CDK4/6 inhibitors and a CDK6-specific degrader, promoting a shift toward more mature interneuron-like states, reducing tumor growth, and prolonging xenograft survival. Notably, a patient with progressive DHG-H3G34 treated with a CDK4/6 inhibitor achieved 17 months of stable disease. This study underscores interneuronal progenitor-like states, organized in characteristic niches, as a distinct vulnerability in DHG-H3G34, highlighting CDK6 as a promising clinically actionable target.",
  "journal": "Cancer Cell",
  "year": 2024,
  "authors": "[\"Liu Ilon\", \"Alencastro Veiga Cruzeiro Gustavo\", \"Bjerke Lynn\", \"Rogers Rebecca F\", \"Grabovska Yura\"]",
  "url": "https://doi.org/10.1016/j.ccell.2024.08.006",
  "external_ids": {
    "doi": "10.1016/j.ccell.2024.08.006",
    "pmid": "39232581",
    "pmcid": "",
    "openalex": "W4402169294",
    "orcid_author": "0000-0001-9012-6552"
  },
  "citation_count": 46
}