Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma.
Cancer Lett
; 593: 216956, 2024 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-38735381
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Xenograft Model Antitumor Assays
/
Protein Kinase Inhibitors
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6
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STAT3 Transcription Factor
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Squamous Cell Carcinoma of Head and Neck
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Head and Neck Neoplasms
Language:
En
Journal:
Cancer Lett
/
Cancer lett
/
Cancer letters
Year:
2024
Document type:
Article
Country of publication:
Irlanda