2. Academic Validation
  3. Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma

Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma

  • Cancer Lett. 2024 May 11:593:216956. doi: 10.1016/j.canlet.2024.216956.
Lin Dong 1,  Chao Liu 1,  Haoyang Sun 2,  Mo Wang 3,  Mengyu Sun 1,  Jianwei Zheng 3,  Xiaoxue Yu 2,  Rong Shi 2,  Bo Wang 1,  Qianqian Zhou 1,  Zhiqiang Chen 1,  Bofan Xing 1,  Yu Wang 1,  Xiaofeng Yao 1,  Mei Mei 4,  Yu Ren 5,  Xuan Zhou 6
Affiliations

Affiliations

  • 1 Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China.
  • 2 Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
  • 3 Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.
  • 4 Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. Electronic address: meim@tmu.edu.cn.
  • 5 Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China; Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China. Electronic address: yuren0925@tmu.edu.cn.
  • 6 Department of Maxillofacial and Otorhinolaryngological Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, China; Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, 300060, China; National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin, 300060, China. Electronic address: xuanzhou@tmu.edu.cn.
PMID: 38735381 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.

Keywords

CDK4/6 inhibitor; Drug sensitivity; Head and neck squamous cell carcinoma; RB; STAT3 activity.

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