{
  "abstract": "The clinical interpretation of rare genomic alterations remains a major challenge in precision oncology, particularly in pediatric cancers. We describe a relapsed high-risk neuroblastoma harboring biallelic BAX inactivation, caused by a pathogenic mutation in one allele (p.E41Gfs*33) and loss of the second, resulting in complete tumor BAX deficiency. To clarify the functional and therapeutic implications of this alteration, BAX-deficient neuroblastoma models were generated and systematically analyzed. Despite complete BAX loss, tumor cells remained sensitive to conventional chemotherapy and to the BCL-2 inhibitor venetoclax, displaying delayed yet preserved cell growth arrest and apoptotic activation. Mechanistic analyses revealed partial compensatory BAK-mediated apoptosis, while combined BAX/BAK depletion suppressed caspase activity and uncovered features consistent with caspase-independent cell death. Together, these findings demonstrate that BAX loss alone does not confer chemoresistance and underscore the importance of functional validation to refine genomic-driven treatment decisions in precision pediatric oncology.",
  "abstract_shown": true,
  "affiliations": [
    "Childhood Cancer and Blood Disorders Group, Vall Hebron Research Institute, Instituto de Investigación Sanitaria Hospital Universitari Vall d’Hebron (IIS IR-HUVH)",
    "Pathology Department, Hospital Vall d’Hebron, Instituto de Investigación Sanitaria Hospital Universitari Vall d’Hebron (IIS IR-HUVH)",
    "Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Adrià Molero-Valenzuela"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabel de Rojas-P"
    },
    {
      "affs": [
        0
      ],
      "name": "Guillem Pons"
    },
    {
      "affs": [
        0
      ],
      "name": "María José Pérez-García"
    },
    {
      "affs": [
        0
      ],
      "name": "Gabriela Guillén"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea Vilaplana"
    },
    {
      "affs": [
        0
      ],
      "name": "Sergio Manresa-Vera"
    },
    {
      "affs": [
        0
      ],
      "name": "Paula Pérez-Albert"
    },
    {
      "affs": [
        1
      ],
      "name": "Marta Garrido"
    },
    {
      "affs": [
        0
      ],
      "name": "Lorena Valero-Arrese"
    },
    {
      "affs": [
        0
      ],
      "name": "Raquel Hladun"
    },
    {
      "affs": [
        2
      ],
      "name": "Mònica Sánchez-Guixé"
    },
    {
      "affs": [
        0
      ],
      "name": "Marta Miera-Maluenda"
    },
    {
      "affs": [
        0
      ],
      "name": "Ariadna Boloix"
    },
    {
      "affs": [
        0
      ],
      "name": "Josep Roma"
    },
    {
      "affs": [
        0
      ],
      "name": "Aroa Soriano"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucas Moreno"
    },
    {
      "affs": [
        0
      ],
      "name": "Miguel F. Segura"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/92vcsk42my7b7.bib",
  "cited_by": 0,
  "doi": "10.1038/s41698-026-01585-w",
  "fulltext_url": "https://doi.org/10.1038/s41698-026-01585-w",
  "id": "92vcsk42my7b7",
  "issns": [
    "2397-768X"
  ],
  "landing_url": "https://doi.org/10.1038/s41698-026-01585-w",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "2728|Neuroblastoma Research and Treatments"
    ]
  ],
  "openalex": "W7167065365",
  "pdf_url": "https://www.nature.com/articles/s41698-026-01585-w_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/92vcsk42my7b7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:36Z",
      "native_id": "970140bc2e344dbdba30b8b95e231e49",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41698-026-01585-w"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Neuroblastoma Research and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Loss of BAX in a neuroblastoma patient reveals delayed apoptosis but sustained chemotherapy sensitivity",
  "title_text": "Loss of BAX in a neuroblastoma patient reveals delayed apoptosis but sustained chemotherapy sensitivity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:36Z",
  "url": "https://research.draconitic.com/paper/92vcsk42my7b7",
  "venue": "npj Precision Oncology",
  "versions": []
}