6533b7cffe1ef96bd12598de

RESEARCH PRODUCT

Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.

Giuseppe MontaltoJörg BäseckeFerdinando NicolettiMelchiorre CervelloMaria Clorinda MazzarinoJames A. MccubreyAlberto M. MartelliDanijela Maksimović-ivanićMassimo LibraCamilla EvangelistiSaverio CandidoPaolo FagoneSanja MijatovićFrancesca ChiariniLinda S. SteelmanGrazia MalaponteStephen L. AbramsWilliam H. ChappellAgostino TafuriMichele MilellaLucio Cocco

subject

MAPK/ERK pathwayPremature agingMAP Kinase Signaling SystemTargeted Therapy Therapy Resistance Mutations Raf Akt PI3K mTORMtorReviewsPi3kPI3KReceptor tyrosine kinaseAkt; Mtor; Mutations; Pi3k; Raf; Targeted therapy; Therapy resistance;Targeted therapyPhosphatidylinositol 3-Kinases03 medical and health sciences0302 clinical medicineAnimalsHumansPTENExtracellular Signal-Regulated MAP KinasesProtein kinase BPI3K/AKT/mTOR pathway030304 developmental biology0303 health sciencesbiologyChemistryTOR Serine-Threonine KinasesAktTherapy resistancePTEN PhosphohydrolaseTargeted TherapyTherapy ResistanceRafProtein phosphatase 2MAP Kinase Kinase Kinases3. Good healthCell biologyOncology030220 oncology & carcinogenesisMutationras ProteinsmTORCancer researchbiology.proteinraf KinasesMitogen-Activated Protein KinasesSignal transductionProto-Oncogene Proteins c-aktMutationsSignal Transduction

description

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Certain components of these pathways, RAS, NF1, BRAF, MEK1, DUSP5, PP2A, PIK3CA, PIK3R1, PIK3R4, PIK3R5, IRS4, AKT, NFKB1, MTOR, PTEN, TSC1, and TSC2 may also be activated/inactivated by mutations or epigenetic silencing. Upstream mutations in one signaling pathway or even in downstream components of the same pathway can alter the sensitivity of the cells to certain small molecule inhibitors. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of components of these cascades can contribute to: resistance to other pathway inhibitors, chemotherapeutic drug resistance, premature aging as well as other diseases. This review will first describe these pathways and discuss how genetic mutations and epigenetic alterations can result in resistance to various inhibitors. Italian Ministero dellIstruzione, dellUniversita e della Ricerca (Ministry for Education, Universities and Research) - MIUR [n. RBNE08YYBM]; CNR from Italian Ministry of Economy and Finance for the Project FaReBio di Qualita; MIUR [RBAP10447J-003, RBA

yearjournalcountryeditionlanguage
2012-01-01Oncotarget
https://doi.org/10.18632/oncotarget.652