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Clinical relevance and therapeutic predictive ability of hypoxia biomarkers in head and neck cancer tumour models.
Lee, Tet Woo; Singleton, Dean C; Harms, Julia K; Lu, Man; McManaway, Sarah P; Lai, Amy; Tercel, Moana; Pruijn, Frederik B; Macann, Andrew M J; Hunter, Francis W; Wilson, William R; Jamieson, Stephen M F.
Afiliación
  • Lee TW; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Singleton DC; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, New Zealand.
  • Harms JK; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Lu M; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, New Zealand.
  • McManaway SP; Department of Molecular Medicine and Pathology, University of Auckland, New Zealand.
  • Lai A; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Tercel M; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Pruijn FB; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Macann AMJ; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Hunter FW; Department of Pharmacology and Clinical Pharmacology, University of Auckland, New Zealand.
  • Wilson WR; Auckland Cancer Society Research Centre, University of Auckland, New Zealand.
  • Jamieson SMF; Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, New Zealand.
Mol Oncol ; 18(8): 1885-1903, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38426642
ABSTRACT
Tumour hypoxia promotes poor patient outcomes, with particularly strong evidence for head and neck squamous cell carcinoma (HNSCC). To effectively target hypoxia, therapies require selection biomarkers and preclinical models that can accurately model tumour hypoxia. We established 20 patient-derived xenograft (PDX) and cell line-derived xenograft (CDX) models of HNSCC that we characterised for their fidelity to represent clinical HNSCC in gene expression, hypoxia status and proliferation and that were evaluated for their sensitivity to hypoxia-activated prodrugs (HAPs). PDX models showed greater fidelity in gene expression to clinical HNSCC than cell lines, as did CDX models relative to their paired cell lines. PDX models were significantly more hypoxic than CDX models, as assessed by hypoxia gene signatures and pimonidazole immunohistochemistry, and showed similar hypoxia gene expression to clinical HNSCC tumours. Hypoxia or proliferation status alone could not determine HAP sensitivity across our 20 HNSCC and two non-HNSCC tumour models by either tumour growth inhibition or killing of hypoxia cells in an ex vivo clonogenic assay. In summary, our tumour models provide clinically relevant HNSCC models that are suitable for evaluating hypoxia-targeting therapies; however, additional biomarkers to hypoxia are required to accurately predict drug sensitivity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Ensayos Antitumor por Modelo de Xenoinjerto / Carcinoma de Células Escamosas de Cabeza y Cuello / Neoplasias de Cabeza y Cuello Límite: Animals / Humans Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biomarcadores de Tumor / Ensayos Antitumor por Modelo de Xenoinjerto / Carcinoma de Células Escamosas de Cabeza y Cuello / Neoplasias de Cabeza y Cuello Límite: Animals / Humans Idioma: En Revista: Mol Oncol Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: Nueva Zelanda Pais de publicación: Estados Unidos