%0 Journal Article
%T Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma.
%A Dong L
%A Liu C
%A Sun H
%A Wang M
%A Sun M
%A Zheng J
%A Yu X
%A Shi R
%A Wang B
%A Zhou Q
%A Chen Z
%A Xing B
%A Wang Y
%A Yao X
%A Mei M
%A Ren Y
%A Zhou X
%J Cancer Lett
%V 593
%N 0
%D 2024 Jul 1
%M 38735381
%F 9.756
%R 10.1016/j.canlet.2024.216956
%X 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.