Significance of mammalian target of rapamycin in patients with locally advanced stage IV head and neck squamous cell carcinoma receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil.

Abstract

This study evaluated the significance of mammalian target of rapamycin (mTOR) activation on the prognosis of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) receiving induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF). Immunohistochemistry (IHC) for phosphorylated-mTOR and phosphorylated-p70 ribosomal S6 protein kinase (p70S6K) examined in 107 patients with locally advanced HNSCC receiving TPF was correlated with treatment outcome. The effect of mTOR inhibition on HNSCC cell lines was investigated in vitro and in vivo. Phosphorylated-mTOR expression was independently significantly associated with response to TPF, progression-free survival (PFS), and overall survival (OS). In cell lines and xenograft models, mTOR inhibitor, everolimus, enhanced the effect of docetaxel. In patients with locally advanced HNSCC treated with TPF, phosphorylated-mTOR expression was independently associated with prognosis. In vitro and in vivo, concomitant inhibition of mTOR enhanced the effect of docetaxel. Our findings suggest the potential of mTOR as a therapeutic target for locally advanced HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E844-E852, 2016.