MEK in cancer and cancer therapy

Pharmacology & Therapeutics
Cindy NeuzilletEric Raymond


The mitogen-activated extracellular signal-regulated kinase (MEK) pathway is one of the best-characterized kinase cascades in cancer cell biology. It is triggered by either growth factors or activating mutations of major oncogenic proteins in this pathway, the most common being Ras and Raf. Deregulation of this pathway is frequently observed and plays a central role in the carcinogenesis and maintenance of several cancers, including melanoma, pancreatic, lung, colorectal, and breast cancers. Targeting these kinases offers promise of novel therapies. MEK inhibitors (MEKi) are currently under evaluation in clinical trials and many have shown activity. In this review, we comprehensively examine the role of the MEK pathway in carcinogenesis and its therapeutic potential in cancer patients, with a focus on MEKi. We describe the clinical perspectives of MEKi in the two main models of Ras-ERK driven tumors, BRAF-mutant ("addicted" to the pathway) and KRAS-mutant (non-"addicted"). We also highlight the known mechanisms of resistance to MEKi and emerging strategies to overcome it.


Apr 16, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y ItoM Hori
Aug 17, 2000·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·K Roovers, R K Assoian
Oct 26, 2000·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J HayashiO Hino
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
May 22, 2003·The American Journal of Pathology·Toru FurukawaAkira Horii
Jun 7, 2003·Nature Cell Biology·Lindsey A AllanPaul R Clarke
Sep 13, 2003·Cancer Letters·Norihisa IshimuraYoshikazu Kinoshita
Jan 7, 2004·Cancer Cell·Sunil R HingoraniDavid A Tuveson
Oct 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John RinehartMark B Meyer
Dec 2, 2004·Molecular and Cellular Biology·Amer M MirzaMartin McMahon
Dec 2, 2004·Nature Reviews. Cancer·Judith S Sebolt-Leopold, Roman Herrera
Dec 16, 2004·Annals of Oncology : Official Journal of the European Society for Medical Oncology·J-P SpanoP Wind
May 6, 2005·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L RepettoP Gazzaniga
Jul 13, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patricia M LorussoMark B Meyer
Nov 8, 2005·Nature·David B SolitNeal Rosen
May 17, 2006·Genes & Development·Aram F HezelRonald A Depinho
Nov 28, 2006·Biochimica Et Biophysica Acta·James A McCubreyRichard A Franklin
Apr 13, 2007·Biochimica Et Biophysica Acta·Krishnaraj RajalingamStefan Albert
May 15, 2007·Oncogene·A S DhillonW Kolch
Mar 8, 2008·Current Opinion in Genetics & Development·Jeffrey A Engelman, Jeffrey Settleman
Jun 20, 2008·The International Journal of Biochemistry & Cell Biology·Joe W Ramos
Jul 25, 2008·Nature Reviews. Cancer·Gabriele Bergers, Douglas Hanahan
Aug 23, 2008·Investigative Ophthalmology & Visual Science·Michael D OnkenJ William Harbour
Oct 11, 2008·Cell Death and Differentiation·K Balmanno, S J Cook
Dec 17, 2008·Nature·Catherine D Van RaamsdonkBoris C Bastian
Feb 17, 2009·Cancer Letters·Clara Montagut, Jeff Settleman
Jul 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Klaus P HoeflichMark R Lackner
Aug 20, 2009·Current Topics in Medicinal Chemistry·Kimberly BurkhardPaul Shapiro
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Martin L SosRoman K Thomas
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Caroline M EmeryLevi A Garraway
Nov 26, 2009·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Wenhu HuangHusam S Younis
Jan 16, 2010·Cancer Investigation·Apar Kishor Ganti
Jan 19, 2010·Biochimica Et Biophysica Acta·Eun Kyung Kim, Eui-Ju Choi
Jan 27, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Alberto Bardelli, Salvatore Siena
Feb 16, 2010·Expert Opinion on Emerging Drugs·James A McCubreyMelchiorre Cervello

❮ Previous
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Jun 8, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Francesca Carlomagno, Mario Chiariello
May 24, 2014·British Journal of Cancer·N CihoricC Tapia
Aug 28, 2015·Expert Review of Anticancer Therapy·Asa Dahle-Smith, Russell D Petty
Jun 5, 2014·Expert Opinion on Drug Discovery·Koh MiuraTsuneaki Fujiya
Feb 11, 2016·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M NicośJ Milanowski
Nov 19, 2015·Pediatric Blood & Cancer·Dolly AguileraTobey J MacDonald
Jan 19, 2016·Investigational New Drugs·Izabella Thaís SilvaCláudia Maria Oliveira Simões
Oct 13, 2015·Life Sciences·Kasi Pandima DeviSeyed Mohammad Nabavi
Oct 27, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Shravan Kumar SriramanVladimir Torchilin
Feb 10, 2016·Trends in Cancer·Meagan B RyanAdrienne D Cox
Jun 6, 2015·Cytokine·Gang HanChengjun Li
Sep 1, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Neil A RobertsAdrian S Woolf
Apr 3, 2015·European Journal of Clinical Investigation·Bénédicte Delire, Peter Stärkel
Aug 25, 2015·Pharmacology & Therapeutics·Cindy NeuzilletPascal Hammel
Jun 30, 2015·Cell·Cathy SlackLinda Partridge
Aug 6, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Xu HouHaiquan Qiao
Jul 30, 2015·Clinical and Translational Medicine·Haiyun WangFan Zhang
Jun 30, 2015·Bulletin du cancer·Pascal HammelOlivia Hentic
Feb 19, 2015·Archives of Toxicology·Eun Kyung Kim, Eui-Ju Choi
Mar 31, 2015·Genes & Diseases·Kyle Knickelbein, Lin Zhang
Apr 1, 2015·Future Medicinal Chemistry·Zutao YuQianbin Li
May 4, 2016·Annals of Oncology : Official Journal of the European Society for Medical Oncology·D M Gershenson
May 18, 2016·Ophthalmic Surgery, Lasers & Imaging Retina·Daniel P NolanSeenu M Hariprasad
Sep 7, 2016·Breast Cancer Research and Treatment·Dena A J AhmadEmad A Rakha
Nov 22, 2016·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Hiroyuki ChoSeiki Hasegawa
Sep 29, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ying Cheng, Hongqi Tian
Dec 6, 2018·Journal of Cellular and Molecular Medicine·Biao GengXingwu Chen
Jan 19, 2019·Journal of Personalized Medicine·David J Hermel, Darren Sigal

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