title: mTOR as a therapeutic target in patients with gastric cancer.
abstract: The poor long-term outcomes associated with current chemotherapy treatment of patients with advanced gastric cancer suggest a need for novel targeted agents that may confer a better survival benefit. Evidence of mammalian target of rapamycin (mTOR) activation has been demonstrated in patient-derived gastric cancer cells and tumors. This review explores the relevance of the mTOR pathway to gastric cancer pathogenesis and its potential as a therapeutic target in patients with gastric cancer as well as presenting the first available clinical data on mTOR inhibitors in this disease setting. Preclinical data suggest that suppression of the mTOR pathway inhibited the proliferation of gastric cancer cells and delayed tumor progression in in vitro and animal models. In the clinical setting, the mTOR inhibitor everolimus has been active and well tolerated in phase I/II studies of patients with chemotherapy-refractory metastatic gastric cancer. Based on these promising results, everolimus currently is being investigated as a monotherapy or in combination with chemotherapeutic agents in ongoing phase II/III clinical studies.
authors: Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt, Germany. albatran@aol.com
authors: Salah-Eddin
authors: SE
authors: Al-Batran
authors: Michel
authors: M
authors: Ducreux
authors: Atsushi
authors: A
authors: Ohtsu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068338:Everolimus; D006801:Humans; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus