Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance
2012
Аутори:
McCubrey, James ASteelman, Linda S
Chappell, William H
Abrams, Stephen L
Franklin, Richard A
Montalto, Giuseppe
Cervello, Melchiorre
Libra, Massimo
Candido, Saverio
Malaponte, Graziella
Mazzarino, Maria C
Fagone, Paolo
Nicoletti, Ferdinando
Baesecke, Joerg
Mijatović, Sanja
Maksimović-Ivanić, Danijela
Milella, Michele
Tafuri, Agostino
Chiarini, Francesca
Evangelisti, Camilla
Cocco, Lucio
Martelli, Alberto M
Тип документа:
Приказ (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). Targeting these pathways is often complex and can result in pathway activation depending on the presence of upstream mutations (e.g., Raf inhibitors induce Raf activation in cells with wild type (WT) RAF in the presence of mutant, activated RAS) and rapamycin can induce Akt activation. Targeting with inhibitors directed at two constituents of the same pathway or two different signaling pathways may be a more effective approach. This review will first evaluate potential uses of Raf, MEK, PI3K, Akt and mTOR inhibitors that have been investigated in pre-clinical and clinical investigations and then discuss how cancers can become insensitive to various inhibitors and potential strategies to overcome this resistance.
Извор:
Oncotarget, 2012, 3, 10, 389-1111
DOI: 10.18632/oncotarget.659
ISSN: 1949-2553
PubMed: 23085539