Version 1
: Received: 6 February 2024 / Approved: 8 February 2024 / Online: 8 February 2024 (14:11:24 CET)
How to cite:
Dan, H.; Geng, X.; Azarbarzin, S.; Yang, Z.; Lapidus, R.G.; Fan, X.; Teng, Y.; Mehra, R.; Cullen, K.J. Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma. Preprints2024, 2024020503. https://doi.org/10.20944/preprints202402.0503.v1
Dan, H.; Geng, X.; Azarbarzin, S.; Yang, Z.; Lapidus, R.G.; Fan, X.; Teng, Y.; Mehra, R.; Cullen, K.J. Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma. Preprints 2024, 2024020503. https://doi.org/10.20944/preprints202402.0503.v1
Dan, H.; Geng, X.; Azarbarzin, S.; Yang, Z.; Lapidus, R.G.; Fan, X.; Teng, Y.; Mehra, R.; Cullen, K.J. Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma. Preprints2024, 2024020503. https://doi.org/10.20944/preprints202402.0503.v1
APA Style
Dan, H., Geng, X., Azarbarzin, S., Yang, Z., Lapidus, R.G., Fan, X., Teng, Y., Mehra, R., & Cullen, K.J. (2024). Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma. Preprints. https://doi.org/10.20944/preprints202402.0503.v1
Chicago/Turabian Style
Dan, H., Ranee Mehra and Kevin J. Cullen. 2024 "Evaluation of Co-Inhibition of ErbB Family and PI3K Kinases for HPV-Negative Head and Neck Squamous Cell Carcinoma" Preprints. https://doi.org/10.20944/preprints202402.0503.v1
Abstract
The ErbB/HER family of protein-tyrosine kinases (ErbB) and the phosphatidylinositol 3-kinase (PI3K) represent crucial targets in the treatment of head and neck squamous cell carcinoma (HNSCC). We previously reported that a combination therapy using Afatinib (ErbB inhibitor) and Copanlisib (PI3K inhibitor), both FDA-approved kinase inhibitors, suppressed the growth of HPV-positive HNSCC. In our current study, we further evaluated the efficacy and clinical potential of this combination therapy for treating HPV-negative HNSCC in vitro and in animal model. We found that the combination treatment of Afatinib and Copanlisib dramatically enhanced inhibition of cell proliferation and reduced cell survival when compared to treatment with either inhibitor in two HPV negative HNSCC cell lines. Notably, this combination led to significant inhibition of xenograft tumor growth in mice, without any apparent effects on body weight. Copanlisib alone effectively blocked PI3K/Akt signaling, but caused up-regulation of HER2 and HER3 phosphorylation as previously reported in other types of cancer. However, the combination treatment with Copanlisib and Afatinib completely blocked phosphorylation of the ErbB family (including HER3) and Akt, while also remarkedly increasing apoptosis. These results suggest that co-targeting the ErbB family and PI3K kinases by a combination treatment of Afatinib and Copanlisib can have clinical potential for patients.
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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