Emerging MEK inhibitors.
BACKGROUND
The Ras/Raf/MEK/ERK pathway is often activated by genetic alterations in upstream signaling molecules. Integral components of this pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK pathway has profound effects on proliferative, apoptotic and differentiation pathways. This pathway can often be effectively silenced by MEK inhibitors. AREAS COVERED BY THIS REVIEW: This review will discuss targeting of MEK which could lead to novel methods to control abnormal proliferation which arises in cancer and other proliferative diseases. This review will cover the scientific literature from 1980 to present and is a follow on from a review which focused on Emerging Raf Inhibitors published in this same review series.


RESULTS
By reading this review the reader will understand the important roles that genetics play in the response of patients to MEK inhibitors, the potential of combining MEK inhibitors with other types of therapy, the prevention of cellular aging and the development of cancer stem cells.


CONCLUSIONS
Targeting MEK has been shown to be effective in suppressing many important pathways involved in cell growth and the prevention of apoptosis. MEK inhibitors have many potential therapeutic uses in the suppression of cancer, proliferative diseases and aging.
McCubrey
James A
JA
Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA. mccubreyj@ecu.edu
Steelman
Linda S
LS
Abrams
Steven L
SL
Chappell
William H
WH
Russo
Suzanne
S
Ove
Roger
R
Milella
Michele
M
Tafuri
Agostino
A
Lunghi
Paolo
P
Bonati
Antonio
A
Stivala
Franca
F
Nicoletti
Ferdinando
F
Libra
Massimo
M
Martelli
Alberto M
AM
Montalto
Giuseppe
G
Cervello
Melchiorre
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D015507:Drugs, Investigational / Q000627:therapeutic use*; D004789:Enzyme Activation; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D015507:Drugs, Investigational; D047428:Protein Kinase Inhibitors; D020930:MAP Kinase Kinase Kinases