{Reference Type}: Journal Article
{Title}: Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma.
{Author}: Dong L;Liu C;Sun H;Wang M;Sun M;Zheng J;Yu X;Shi R;Wang B;Zhou Q;Chen Z;Xing B;Wang Y;Yao X;Mei M;Ren Y;Zhou X;
{Journal}: Cancer Lett
{Volume}: 593
{Issue}: 0
{Year}: 2024 Jul 1
{Factor}: 9.756
{DOI}: 10.1016/j.canlet.2024.216956
{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.