Clinical Cancer Research CR Surrogrates Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online

Clinical Cancer Research 14, 342, January 15, 2008. doi: 10.1158/1078-0432.CCR-07-4790
© 2008 American Association for Cancer Research

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Friday, B. B.
Right arrow Articles by Adjei, A. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Friday, B. B.
Right arrow Articles by Adjei, A. A.

Molecular Pathways

Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy

Bret B. Friday1 and Alex A. Adjei2

Authors' Affiliations: 1 Department of Oncology, Mayo Clinic, Rochester, Minnesota and 2 Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Alex A. Adjei, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: 716-845-4101; Fax: 716-845-3423; E-mail: Alex.Adjei{at}RoswellPark.org.

Abstract

The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently, several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling, have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials.




This article has been cited by other articles:


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Basu, R. Harfouche, S. Soni, G. Chimote, R. A. Mashelkar, and S. Sengupta
Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy
PNAS, May 12, 2009; 106(19): 7957 - 7961.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
H. Wong, M. Belvin, S. Herter, K. P. Hoeflich, L. J. Murray, L. Wong, and E. F. Choo
Pharmacodynamics of 2-{4-[(1E)-1-(Hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl}ethan-1-ol (GDC-0879), a Potent and Selective B-Raf Kinase Inhibitor: Understanding Relationships between Systemic Concentrations, Phosphorylated Mitogen-Activated Protein Kinase Kinase 1 Inhibition, and Efficacy
J. Pharmacol. Exp. Ther., April 1, 2009; 329(1): 360 - 367.
[Abstract] [Full Text] [PDF]


Home page
Molecular Cancer TherapeuticsHome page
J. J. Yeh, E. D. Routh, T. Rubinas, J. Peacock, T. D. Martin, X. J. Shen, R. S. Sandler, H. J. Kim, T. O. Keku, and C. J. Der
KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer
Mol. Cancer Ther., April 1, 2009; 8(4): 834 - 843.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
M. W. VanBrocklin, M. Verhaegen, M. S. Soengas, and S. L. Holmen
Mitogen-Activated Protein Kinase Inhibition Induces Translocation of Bmf to Promote Apoptosis in Melanoma
Cancer Res., March 1, 2009; 69(5): 1985 - 1994.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
F. Di Nicolantonio, M. Martini, F. Molinari, A. Sartore-Bianchi, S. Arena, P. Saletti, S. De Dosso, L. Mazzucchelli, M. Frattini, S. Siena, et al.
Wild-Type BRAF Is Required for Response to Panitumumab or Cetuximab in Metastatic Colorectal Cancer
J. Clin. Oncol., December 10, 2008; 26(35): 5705 - 5712.
[Abstract] [Full Text] [PDF]


Home page
BloodHome page
K. R. Calvo, B. Dabir, A. Kovach, C. Devor, R. Bandle, A. Bond, J. H. Shih, and E. S. Jaffe
IL-4 protein expression and basal activation of Erk in vivo in follicular lymphoma
Blood, November 1, 2008; 112(9): 3818 - 3826.
[Abstract] [Full Text] [PDF]


Home page
Am Soc Clin Oncol Ed BookHome page
S. Turcotte and A. J. Giaccia
Targeted Therapy for the Loss of the Tumor Suppressor Gene von Hippel-Lindau through Synthetic Lethality
ASCO Educational Book, January 1, 2008; 2008(1): e15 - e18.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.