We thank the participants and research staff who made the study possible. Footnotes Competing Interests: The sellckchem authors have declared that no competing interests exist. Funding: This work was supported by the National Institute of Health grant numbers KO1 TW006087, funded by the Fogarty International Center; R01 DK082766, funded by National Institute of
Oesophageal squamous cell carcinoma (OSCC), the major histological type of oesophageal cancer in East Asian countries, is one of the most aggressive malignant tumours (Enzinger and Mayer, 2003). Despite the development of multimodal therapies, including surgery, chemotherapy, and radiotherapy, the prognosis remains poor even for patients who undergo complete carcinoma resection.
The limited improvement in outcomes achieved by conventional therapies urges us to seek innovative strategies, especially those involving molecular targeting, for treating OSCC. The mammalian target of rapamycin (mTOR) is a 289-kDa serine/threonine kinase involved in cellular growth and homeostasis (Bjornsti and Houghton, 2004; Abraham and Gibbons, 2007; Menon and Manning, 2008; Wouters and Koritzinsky, 2008). Mammalian target of rapamycin is activated by phosphorylation as a part of the phosphatidylinositol-3 kinase/AKT signalling pathway (Mita et al, 2003; Chan, 2004; Dancey, 2006) and in turn phosphorylates and activates eukaryotic translation factor 4E (elF4E) and p70 ribosomal S6 kinase (p70S6 kinase), leading to the translation of proteins required for cell cycle progression (Hidalgo and Rowinsky, 2000; Panwalkar et al, 2004).
The presence and prognostic significance of aberrant mTOR activation have been reported for several types of human carcinomas (Easton and Houghton, 2006; Herberger et al, 2007; Hou et al, 2007; Hudes, 2009; Hirashima et al, 2010). Our group previously showed an association between high phosphorylated mTOR (p-mTOR) expression and poor prognosis in 143 resected OSCC samples (Hirashima et al, 2010). Mammalian target of rapamycin has recently been recognised as an important and attractive target for anti-cancer therapy (Boulay et al, 2004; Bianco et al, 2006; Johnston, 2006; Antonarakis et al, 2010; Sparks and Guertin, 2010). Everolimus, an oral mTOR inhibitor, has shown particularly promising results in experimental studies, inhibiting tumour growth and displaying anti-angiogenic effects (Carmeliet and Jain, 2000; Bianco et al, 2008; Manegold et al, 2008; Lane et al, 2009).
Combination therapy using everolimus and cisplatin has also been reported to be effective (Beuvink et al, 2005; Mabuchi et al, 2007; Hou et al, 2010; Ma et al, 2010). Many clinical trials using everolimus for several types of cancers are currently underway (Yee et al, 2006; Fouladi et al, 2007; Gridelli Entinostat et al, 2007; Johnson et al, 2007; Awada et al, 2008; O’Donnell et al, 2008; Tabernero et al, 2008; Tanaka et al, 2008; Yao et al, 2008; Wolpin et al, 2009).