Mutations and Deregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascades Which Alter Therapy Response.
2012
Аутори:
McCubrey, James ASteelman, Linda S
Chappell, William H
Abrams, Stephen L
Montalto, Giuseppe
Cervello, Melchiorre
Nicoletti, Ferdinando
Fagone, Paolo
Malaponte, Graziella
Mazzarino, Maria C
Candido, Saverio
Libra, Massimo
Baesecke, Joerg
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Milella, Michele
Tafuri, Agostino
Cocco, Lucio
Evangelisti, Camilla
Chiarini, Francesca
Martelli, Alberto M
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
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.
Извор:
Oncotarget, 2012, 3, 9, 153-987
DOI: 10.18632/oncotarget.652
ISSN: 1949-2553
PubMed: 23006971