Abstract：
Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.
摘要：
抗CDK4/6疗法已用于治疗CDK4/6过度激活的头颈部鳞状细胞癌（HNSCC），但是应答率相对较低。在这项研究中,我们首先发现CDK4和CDK6在HNSCC中过度表达并导致预后不良。此外，在RB阳性HNSCC中，STAT3信号传导被CDK4/6抑制激活，STAT3通过上调MYC促进RB缺乏。第三，Stattic和CDK4/6抑制剂的组合在体外和Cal27衍生的动物模型中产生显著的抗肿瘤作用。此外,磷酸化STAT3水平与RB表达呈负相关，并预测HNSCC患者的不良预后。一起来看,我们的研究结果表明,STAT3的未被识别的功能赋予了CDK4/6抑制剂的耐药性,并为HNSCC患者提供了一个有前景的联合治疗策略.
