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Simultaneously targeting ErbB family kinases and PI3K in HPV-positive head and neck squamous cell carcinoma.
Yang, Zejia; Liao, Jipei; Schumaker, Lisa; Carter-Cooper, Brandon; Lapidus, Rena G; Fan, Xiaoxuan; Gaykalova, Daria A; Mehra, Ranee; Cullen, Kevin J; Dan, Hancai.
Afiliación
  • Yang Z; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Liao J; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Schumaker L; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Carter-Cooper B; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Lapidus RG; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Fan X; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Gaykalova DA; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA; Institute for Genome Sciences, University of Maryland Medical Center, Baltimore, MD, USA; Department of Otorhinolaryngology-Head & Neck Surgery, University of Maryland Schoo
  • Mehra R; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
  • Cullen KJ; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: kcullen@umm.edu.
  • Dan H; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: HDan@som.umaryland.edu.
Oral Oncol ; 131: 105939, 2022 08.
Article en En | MEDLINE | ID: mdl-35667295
OBJECTIVES: To identify the most effective PI3K and EGFR inhibitors in HPV-positive head and neck squamous cell carcinoma (HNSCC) and investigate the efficacy of a combination of an ErbB family kinase inhibitor and a PI3K inhibitor to inhibit cell proliferation of HPV-positive HNSCC. MATERIALS AND METHOD: HPV-positive HNSCC cell lines were treated with the FDA approved ErbB kinase inhibitor, Afatinib or FDA-approved PI3K inhibitor, Copanlisib, alone or in combination, and phosphorylation and total protein levels of cells were assessed by Western blot analysis.Cell proliferation and apoptosis were examined by MTS assay, flow cytometry, and Western blots, respectively. RESULTS: Copanlisib more effectively inhibited cell proliferation in comparison to other PI3K inhibitors tested. HPV-positive HNSCC cells differentially responded to cisplatin, Afatinib, or Copanlisib. The combination of Afatinib and Copanlisib more effectively suppressed cell proliferation and induced apoptosis compared to either treatment alone. Mechanistically, the combination of Afatinib and Copanlisib completely blocked phosphorylation of EGFR, HER2, HER3, and Akt as well as significantly decreased the HPV E7 expression compared to either treatment alone. CONCLUSION: Afatinib and Copanlisib more effectively suppress cell proliferation and survival of HPV-positive HNSCC in comparison to either treatment alone.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Papillomavirus / Neoplasias de Cabeza y Cuello / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Oral Oncol Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones por Papillomavirus / Neoplasias de Cabeza y Cuello / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Oral Oncol Asunto de la revista: NEOPLASIAS Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido