title: Recent developments in anti-cancer agents targeting PI3K, Akt and mTORC1/2.
abstract: Inappropriate PI3K signaling is one of the most frequent occurrences in human cancer and is critical for tumor progression. A variety of genetic mutations and amplifications have been described affecting key components of this pathway, with implications not only for tumorigenesis but also for resistance to targeted agents. Emerging preclinical research has significantly advanced our understanding of the PI3K pathway and its complex downstream signalling, interactions and crosstalk. This knowledge, combined with the limited clinical antitumor activity of mTOR complex 1 inhibitors, has led to the development of rationally designed drugs targeting key elements of this pathway, such as pure PI3K inhibitors (both pan-PI3K and isoform-specific), dual PI3K/ mTOR inhibitors, Akt inhibitors, and mTOR complexes 1 and 2 catalytic site inhibitors. This review will focus primarily on an analysis of newly developed inhibitors of this pathway that have entered clinical trials, and recently registered patents in this field.
authors.affiliation: Medical Oncology Service, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, Universitat Autonoma de Barcelona, Barcelona, 08035, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Dienstmann
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodon
authors.forename: Ben
authors.initials: B
authors.lastname: Markman
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015195:Drug Design; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010330:Patents as Topic; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; C493245:CRTC2 protein, human; D046912:Multiprotein Complexes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011506:Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases