Ribociclib is a specific cyclin dependent kinase (Cdk) 4/6 inhibitor that 
induces G1 arrest by blocking the formation of cyclin D1-Cdk4/6 complex and 
inhibiting retinoblastoma (RB) phosphorylation. Cyclin D1 is overexpressed in 
over 90% of nasopharyngeal carcinoma (NPC) and CCND1 gene activation plays a 
critical role in NPC pathogenesis. This study evaluated the preclinical 
activities of ribociclib in NPC cell lines and patient derived xenograft (PDX) 
models. Over 95% cell growth inhibition was observed at 96 hours after 
ribociclib treatment. (IC50 concentrations: HK1 = 1.42 ± 0.23 µM; 
HK1-LMP1 = 2.18 ± 0.70 µM and C666-1 = 8.26 ± 0.92 µM). HK1 and C666-1 cells 
were chosen for analysis of ribociclib on kinase signaling, apoptosis and cell 
cycle. Treatment with ribociclib for 48 hours consistently showed a 
dose-dependent reduction in phosphorylated and total RB expression and G1 cycle 
arrest was only observed. Combining ribociclib with the alpha-specific PI3K 
inhibitor alpelisib showed a synergistic effect in two NPC PDX models in nude 
mice. The co-treatment induced a significant reduction in tumor volume in both 
xeno-666 and xeno-2117 compared with ribociclib treatment alone and control 
(p < 0.01). In summary, ribociclib is active in NPC models and the effect on 
growth inhibition was augmented when combined with alpelisib. This study 
supports the clinical evaluation of ribociclib in NPC.