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Targeting STAT3 potentiates CDK4/6 inhibitors therapy in head and neck squamous cell carcinoma.
- Source :
-
Cancer Letters . Jul2024, Vol. 593, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
-
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. • CDK4/6 inhibitors result in STAT3 nuclear translocation and activation. • STAT3 promotes RB deficiency by upregulation of MYC in RB-positive cells. • The small molecule inhibitor of STAT3, Stattic acts in synergy with CDK4/6 inhibitors in mouse model. • Phospho-STAT3 activity negatively correlates with RB expression in patients with HNSCC. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043835
- Volume :
- 593
- Database :
- Academic Search Index
- Journal :
- Cancer Letters
- Publication Type :
- Academic Journal
- Accession number :
- 177757109
- Full Text :
- https://doi.org/10.1016/j.canlet.2024.216956