title: Impact of genetic alterations on mTOR-targeted cancer therapy.
abstract: Rapamycin and its derivatives (rapalogs), a group of allosteric inhibitors of mammalian target of rapamycin (mTOR), have been actively tested in a variety of cancer clinical trials, and some have been approved by the Food and Drug Administration for the treatment of certain types of cancers. However, the single agent activity of these compounds in many tumor types remains modest. The mTOR axis is regulated by multiple upstream signaling pathways. Because the genes (e.g., PIK3CA, KRAS, PTEN, and LKB1) that encode key components in these signaling pathways are frequently mutated in human cancers, a subset of cancer types may be addicted to a given mutation, leading to hyperactivation of the mTOR axis. Thus, efforts have been made to demonstrate the potential impact of genetic alterations on rapalog-based or mTOR-targeted cancer therapy. This review will primarily summarize research advances in this direction.
authors.affiliation: Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA. ssun@emory.edu
authors.forename: Shi-Yong
authors.initials: SY
authors.lastname: Sun
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D045744:Cell Line, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000091162:AMP-Activated Protein Kinase Kinases; D000903:Antibiotics, Antineoplastic; D058534:Class I Phosphatidylinositol 3-Kinases; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C546842:MTOR protein, human; C484760:PIK3CA protein, human; C109790:STK11 protein, human; C494929:PTEN protein, human