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.
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.
Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Shau-Hsuan
SH
Li
Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Wei-Che
WC
Lin
Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Tai-Lin
TL
Huang
Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chang-Han
CH
Chen
Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Tai-Jan
TJ
Chiu
Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Fu-Min
FM
Fang
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Wan-Ting
WT
Huang
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Cheng-Ming
CM
Hsu
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Sheng-Dean
SD
Luo
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chi-Chih
CC
Lai
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Yan-Ye
YY
Su
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Hui-Ching
HC
Chuang
Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.|Kaohsiung Chang Gung Head and Neck Oncology Group, Cancer Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Chih-Yen
CY
Chien
D000328:Adult; D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D043823:Taxoids / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D043823:Taxoids; D000077143:Docetaxel; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin; D005472:Fluorouracil
docetaxel; head and neck cancer; induction chemotherapy; mammalian target of rapamycin (mTOR); squamous cell carcinoma