Shau-Hsuan Li1,2, Wei-Che Lin3,2, Tai-Lin Huang1,2, Chang-Han Chen4,2, Tai-Jan Chiu1,2, Fu-Min Fang5,2, Wan-Ting Huang6, Cheng-Ming Hsu7,2, Sheng-Dean Luo7,2, Chi-Chih Lai7,2, Yan-Ye Su7,2, Hui-Ching Chuang7,2, Chih-Yen Chien7,2. 1. Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 2. Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan. 3. Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 4. Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 5. Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 6. Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 7. Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.