TY - JOUR
T1 - Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors
T2 - Rationale and importance to inhibiting these pathways in human health
AU - Chappell, William H.
AU - Steelman, Linda S.
AU - Long, Jacquelyn M.
AU - Kempf, Ruth C.
AU - Abrams, Stephen L.
AU - Franklin, Richard A.
AU - Bäsecke, Jörg
AU - Stivala, Franca
AU - Donia, Marco
AU - Fagone, Paolo
AU - Malaponte, Graziella
AU - Mazzarino, Maria C.
AU - Nicoletti, Ferdinando
AU - Libra, Massimo
AU - Maksimovic-Ivanic, Danijela
AU - Mijatovic, Sanja
AU - Montalto, Giuseppe
AU - Cervello, Melchiorre
AU - Laidler, Piotr
AU - Milella, Michele
AU - Tafuri, Agostino
AU - Bonati, Antonio
AU - Evangelisti, Camilla
AU - Cocco, Lucio
AU - Martelli, Alberto M.
AU - McCubrey, James A.
PY - 2011
Y1 - 2011
N2 - 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). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/ MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.
AB - 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). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/ MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.
KW - Aging
KW - Akt
KW - Cancer stem cells
KW - Combination therapy
KW - Drug resistance
KW - mTOR
KW - Pi3K
KW - Raf
KW - Senescence
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=79959712087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959712087&partnerID=8YFLogxK
M3 - Article
C2 - 21411864
AN - SCOPUS:79959712087
VL - 2
SP - 135
EP - 164
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 3
ER -