6533b856fe1ef96bd12b1cde
RESEARCH PRODUCT
New agents and approaches for targeting the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR cell survival pathways.
Stephen L. AbramsWilliam H. ChappellGiuseppe MontaltoRichard A. FranklinFerdinando NicolettiCamilla EvangelistiAlberto M. MartelliAlberto M. MartelliMelchiorre CervelloLinda S. SteelmanJörg BäseckeClorinda MassarinoMassimo LibraGraziella MalaponteFrancesca ChiariniJames A. MccubreyLucio CoccoMichele MilellaAgostino Tafurisubject
MAPK/ERK pathway0303 health sciencesCell signalingbiologyChemistryAKTApoptosisGrowth factorRafOncogens: Signaling pathway3. Good healthMalignant transformation03 medical and health sciences0302 clinical medicineApoptosis030220 oncology & carcinogenesisCancer researchbiology.proteinEpidermal growth factor receptorSignal transductionpi3kProtein kinase BRaPI3K/AKT/mTOR pathway030304 developmental biologydescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-11-17 |