title: Targeting the PI3K/Akt/mTOR pathway--beyond rapalogs.
abstract: It is well established that the PI3K pathway plays a central role in various cellular processes that can contribute to the malignant phenotype. Accordingly, pharmacological inhibition of key nodes in this signaling cascade has been a focus in developmental therapeutics. To date, agents targeting upstream receptor tyrosine kinases are best studied and have achieved greatest clinical success. Further downstream, despite efficacy in certain tumor types, the rapalogs have been somewhat disappointing in the clinic. Novel inhibitors of PI3K, Akt, and mTORC1 and 2 are now passing through early phase clinical trials. It is hoped that these agents will circumvent some of the shortcomings of the rapalogs and lead to meaningful benefits for cancer patients.
authors.affiliation: Centre for Cancer Research, Monash Institute of Medical Research, Southern Health, Melbourne, Victoria, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Markman
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Dienstmann
authors.affiliation: Medical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000818:Animals; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human