Details

Autor(en) / Beteiligte

• Yang, Zejia
• Liao, Jipei
• Schumaker, Lisa
• Carter-Cooper, Brandon
• Lapidus, Rena G.
• Fan, Xiaoxuan
• Gaykalova, Daria A.
• Mehra, Ranee
• Cullen, Kevin J.
• Dan, Hancai

Titel

Simultaneously targeting ErbB family kinases and PI3K in HPV-positive head and neck squamous cell carcinoma

Ist Teil von

• Oral oncology, 2022-08, Vol.131, p.105939-105939, Article 105939

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• •Identification of the most effective PI3K inhibitors, copanlisib in HPV-positive head and neck squamous cell carcinoma (HNSCC)•Copanlisib, in combination with ErbB inhibitor, afatinib effectively inhibits cell proliferation and survival.•A combination of Copanlisib and afatinib significantly decreased the HPV E7 expression.•This study provides a new therapeutic option to effectively treat patients with HPV positive HNSCC. 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. 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. 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. Afatinib and Copanlisib more effectively suppress cell proliferation and survival of HPV-positive HNSCC in comparison to either treatment alone.