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Ref Type Journal Article
PMID (25682238)
Authors Naruse T, Yanamoto S, Yamada S, Rokutanda S, Kawakita A, Kawasaki G, Umeda M
Title Anti-tumor effect of the mammalian target of rapamycin inhibitor everolimus in oral squamous cell carcinoma.
Journal Vol Issue Date Pages Journal Short Title
Pathology oncology research : POR 21 3 2015 Jul 765-73 Pathol Oncol Res
URL
Abstract Text The mammalian target of rapamycin (mTOR) has recently emerged as a promising target for therapeutic anti-cancer interventions in several human tumors. In present study, we investigated the expression of mTOR, and subsequently examined its relationship with clinicopathological factors and the anti-tumor effect of everolimus (also known as RAD001) in oral squamous cell carcinoma (OSCC). The expression of phosphorylated mTOR (p-mTOR) was immunohistochemically evaluated in specimens obtained from 70 OSCC patients who underwent radical surgery. The relationships between the expression of p-mTOR and clinicopathological factors and survival were determined. We also investigated the effect of everolimus on the OSCC cell lines, SAS, HSC-2, HSC-3, HSC-4, OSC-20, SCC25 and Ca9-22 by the MTT assay. We further evaluated whether mTOR contributed to cell functions by blocking its activity with everolimus, and confirmed the direct target by the Matrigel invasion assay, wound healing assay and Western blotting. p-mTOR was overexpressed in 37 tumors (52.8 %), and correlated with the T classification, N classification, and survival rate (P < 0.05). The treatment with everolimus significantly inhibited cell growth, and significantly reduced the expression of p-mTOR, downstream signaling proteins, and hypoxic related proteins as well as invasion and migration potentials (P < 0.05). The results of the present study suggest that everolimus may represent an attractive approach for the future treatment of OSCC.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References