Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma

• DOI: 10.20944/preprints202402.0503.v1
• Publication Date: 2024-02-09T10:23:16Z
• Authors: Hancai Dan; Xinyan Geng; Shirin Azarbarzin; Zejia Yang; Rena G. Lapidus; Xiaoxuan Fan; Yong Teng; Ranee Mehra; Kevin J. Cullen
• Keywords: ErbB

The ErbB/HER family of protein-tyrosine kinases (ErbB) and the phosphatidylinositol 3-kinase (PI3K) represent crucial targets in treatment head neck squamous cell carcinoma (HNSCC). We previously reported that a combination therapy using Afatinib (ErbB inhibitor) Copanlisib (PI3K inhibitor), both FDA-approved kinase inhibitors, suppressed growth HPV-positive HNSCC. In our current study, we further evaluated efficacy clinical potential this for treating HPV-negative HNSCC vitro animal model. found dramatically enhanced inhibition proliferation reduced survival when compared to with either inhibitor two HPV negative lines. Notably, led significant xenograft tumor mice, without any apparent effects on body weight. alone effectively blocked PI3K/Akt signaling, but caused up-regulation HER2 HER3 phosphorylation as other types cancer. However, completely ErbB (including HER3) Akt, while also remarkedly increasing apoptosis. These results suggest co-targeting PI3K by can have patients.