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RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Simultaneously targeting ErbB family kinases and PI3K in HPV-positive head and neck squamous cell carcinoma
Zejia Yang1, Jipei Liao1, Lisa Schumaker1
1Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
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.
Insights
The combination of Afatinib and Copanlisib effectively inhibits proliferation and induces apoptosis in HPV-positive head and neck squamous cell carcinoma (HNSCC). This dual therapy targets both ErbB and PI3K pathways, offering a promising treatment strategy for HNSCC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) remains a significant health challenge.
- Targeting key signaling pathways like PI3K and EGFR is crucial for effective cancer treatment.
Purpose of the Study:
- To determine the most effective PI3K and EGFR inhibitors for HPV-positive HNSCC.
- To evaluate the combined efficacy of an ErbB family kinase inhibitor and a PI3K inhibitor against HPV-positive HNSCC cell proliferation.
Main Methods:
- HPV-positive HNSCC cell lines were treated with Afatinib (ErbB inhibitor) and Copanlisib (PI3K inhibitor) alone and in combination.
- Cell proliferation, apoptosis, and protein phosphorylation were assessed using MTS assays, flow cytometry, and Western blot analysis.
Main Results:
- Copanlisib demonstrated superior inhibition of cell proliferation compared to other PI3K inhibitors.
- The combination of Afatinib and Copanlisib significantly suppressed cell proliferation and induced apoptosis more effectively than either agent alone.
- Combined treatment completely blocked EGFR, HER2, HER3, and Akt phosphorylation and reduced HPV E7 expression.
Conclusions:
- Afatinib and Copanlisib combination therapy is more effective in suppressing cell proliferation and enhancing survival in HPV-positive HNSCC than monotherapy.
- This combination strategy presents a promising therapeutic approach for HPV-positive HNSCC by targeting critical oncogenic pathways.
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