Article
Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance.
Oncotarget - 1 Oct 2012
McCubrey James A, Steelman Linda S, Chappell William H, Abrams Stephen L, Franklin Richard A, Montalto Giuseppe, Cervello Melchiorre, Libra Massimo, Candido Saverio, Malaponte Grazia, Mazzarino Maria C, Fagone Paolo, Nicoletti Ferdinando, Bäsecke Jörg, Mijatovic Sanja, Maksimovic-Ivanic Danijela, Milella Michele, Tafuri Agostino, Chiarini Francesca, Evangelisti Camilla, Cocco Lucio, Martelli Alberto M
Abstract excerpt
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)...
Topics
- Antineoplastic Agents
- Cell Line, Tumor
- Drug Resistance, Neoplasm
- Extracellular Signal-Regulated MAP Kinases
- Humans
- MAP Kinase Kinase Kinases
- Mutation
- Neoplasms