The mTOR pathway: a new target in cancer therapy.
Mammalian target of rapamycin (mTOR) is a key protein kinase controlling signal transduction from various growth factors and upstream proteins to the level of mRNA translation and ribosome biogenesis, with pivotal regulatory effects on cell cycle progression, cellular proliferation and growth, autophagy and angiogenesis. The mTOR pathway, and its upstream regulators in the PI3K/PTEN/AKT cascade, are altered in a variety of experimental and human malignancies.This has led to the prediction that mTOR inhibitors may be used as anticancer agents. With the recent approval of two mTOR-targeted drugs (temsirolimus and everolimus) for the treatment of renal cell carcinoma and mantle cell lymphoma, this paradigm has been effectively translated into the clinical setting. In this review, we discuss mTOR biology and regulation, the mode of action of mTOR inhibitors as anti-cancer agents, and current clinical evidence supporting the use of rapamycin-like mTOR inhibitors in cancer treatment.
Ciuffreda
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Division of Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi n. 53, 00144 Rome, Italy.
Di Sanza
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C
Incani
U C
UC
Milella
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D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy*; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases