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.
Brody School of Medicine at East Carolina University, Department of Microbiology & Immunology, 600 Moye Boulevard, Greenville, NC 27858, USA. mccubreyj@ecu.edu
James A
JA
McCubrey
Linda S
LS
Steelman
Steven L
SL
Abrams
William H
WH
Chappell
Suzanne
S
Russo
Roger
R
Ove
Michele
M
Milella
Agostino
A
Tafuri
Paolo
P
Lunghi
Antonio
A
Bonati
Franca
F
Stivala
Ferdinando
F
Nicoletti
Massimo
M
Libra
Alberto M
AM
Martelli
Giuseppe
G
Montalto
Melchiorre
M
Cervello
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