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