Evaluation of co-inhibition of ErbB family kinases and PI3K for HPV-negative head and neck squamous cell carcinoma

被引:0
|
作者
Geng, Xinyan [1 ]
Azarbarzin, Shirin [1 ]
Yang, Zejia [1 ]
Lapidus, Rena G. [1 ]
Fan, Xiaoxuan [1 ]
Teng, Yong [2 ]
Mehra, Ranee [1 ]
Cullen, Kevin J. [1 ]
Dan, Hancai [1 ,3 ]
机构
[1] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Comprehens Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA
[2] Emory Univ, Winship Canc Inst, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA 30332 USA
[3] Univ Maryland, Sch Med, Dept Pathol, 655 West Baltimore St, Baltimore, MD 21201 USA
关键词
head and neck squamous cell carcinoma; PI3K inhibitors; ErbB inhibitor; targeted therapies; LOCALLY ADVANCED HEAD; THERAPY LUX-HEAD; 2ND-LINE TREATMENT; HUMAN-PAPILLOMAVIRUS; TARGETED THERAPY; EMERGING DRUGS; OPEN-LABEL; CANCER; AFATINIB; PATHWAY;
D O I
10.3892/or.2025.8871
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The ErbB/HER family of protein-tyrosine kinases and PI3K represent crucial targets in the treatment of head and neck squamous cell carcinoma (HNSCC). A combination therapy of afatinib (ErbB inhibitor) and copanlisib (PI3K inhibitor), both Food and Drug Administration-approved kinase inhibitors, can suppress the growth of human papillomavirus (HPV)-positive HNSCC. The current study further evaluated the efficacy and clinical potential of this combination therapy for the treatment of HPV-negative HNSCC in vitro and in vivo. Sulforhodamine B cell viability assay and Annexin V/propidium iodide staining demonstrated that this combination treatment markedly enhanced inhibition of cell viability and reduced cell survival when compared with treatment with either inhibitor alone in two HPV-negative HNSCC cell lines. Notably, this combination also led to significant inhibition of xenograft tumor growth in mice, without any apparent effects on body weight. Western blot analysis found that copanlisib alone effectively blocked PI3K/Akt signaling but caused upregulation of HER2 and HER3 phosphorylation, as reported in other types of cancer. However, the combination of copanlisib and afatinib completely blocked phosphorylation of the ErbB family (including HER3) and Akt, while also increasing apoptosis. In conclusion, these results suggested that co-targeting the ErbB family kinases and PI3K using a combination treatment of afatinib and copanlisib may have clinical potential for patients with HPV-negative HNSCC.
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页数:11
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