Combination of Epithelial Growth Factor Receptor Blockers and CDK4/6 Inhibitor for Nasopharyngeal Carcinoma Treatment

Cancers

Kar-Wai Lui¹  Hsin-Pai Li²  Yu-Sun Chang²  Mei-Yuan Huang²  Yi-Ru Lai²  Kai-Ping Chang³  Yenlin Huang⁴  Li-Yu Lee⁴  Chien-Yu Lin⁵  An-Chi Lin⁶  Cheng-Lung Hsu⁶  Hsien-Chi Fan⁶  Chen-Yang Huang⁶  Jason Chia-Hsun Hsieh⁶  Hung-Ming Wang⁶  Tung-Liang Lin⁶  Yung-Chia Kuo⁶  Yin-Kai Chao⁷  Yuan-Ming Yeh⁸  Chun-Nan Yeh⁹ 

[1] Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;Department of Microbiology and Immunology, Chang Gung University, Taoyuan 33305, Taiwan;Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;Department of Radiation, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan;Liver Research Center, Department of General Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan 33305, Taiwan;

关键词: NPC;    PDX;    EBV;    EGF;    EGFR blocker;    CDK4/6 inhibitor;   

DOI  :  10.3390/cancers13122954

来源: DOAJ

【 摘 要 】

Background: Nasopharyngeal carcinoma (NPC) involves host genetics, environmental and viral factors. In clinical observations, patients of young and old ages were found to have higher recurrence and metastatic rates. Methods: Cytokine array was employed to screen druggable target(s). The candidate target(s) were confirmed through patient-derived xenografts (PDXs) and a new EBV-positive cell line, NPC-B13. Results: Overexpression of epithelial growth factor (EGF) and EGF receptor (EGFR) was detected in young patients than in older patients. The growth of NPC PDX tumors and cell lines was inhibited by EGFR inhibitors (EGFRi) cetuximab and afatinib when used separately or in combination with the cell cycle blocker palbociclib. Western blot analysis of these drug-treated PDXs demonstrated that the blockade of the EGF signaling pathway was associated with a decrease in the p-EGFR level and reduction in PDX tumor size. RNA sequencing results of PDX tumors elucidated that cell cycle-related pathways were suppressed in response to drug treatments. High EGFR expression (IHC score ≥ grade 3) was correlated with poor survival in metastatic patients (p = 0.008). Conclusions: Our results provide encouraging preliminary data related to the combination treatment of EGFRi and palbociclib in patients with NPC.

【 授权许可】

Unknown