Molecular pathways: response and resistance to BRAF and MEK inhibitors in BRAF(V600E) tumors

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Meghna Das Thakur, Darrin D Stuart

Abstract

The RAS-RAF-MEK (MAP-ERK kinase)-ERK (extracellular signal-regulated kinase) pathway plays a central role in driving proliferation, survival, and metastasis signals in tumor cells, and the prevalence of oncogenic mutations in RAS and BRAF and upstream nodes makes this pathway the focus of significant oncology drug development efforts. This focus has been justified by the recent success of BRAF and MEK inhibitors in prolonging the lives of patients with BRAF(V600E/K)-mutant melanoma. Although it is disappointing that cures are relatively rare, this should not detract from the value of these agents to patients with cancer and the opportunity they provide in allowing us to gain a deeper understanding of drug response and resistance. These insights have already provided the basis for the evaluation of alternative dosing regimens and combination therapies in patients with melanoma.

References

Oct 6, 1995·The Journal of Biological Chemistry·J V BarnierG Calothy
Jul 8, 1999·Nature Medicine·J S Sebolt-LeopoldA R Saltiel
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
Oct 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·John RinehartMark B Meyer
Nov 3, 2004·Nature Reviews. Molecular Cell Biology·Claudia WellbrockRichard Marais
Mar 24, 2005·Cancer Metastasis Reviews·Vanessa C Gray-SchopferRichard Marais
Nov 18, 2005·The New England Journal of Medicine·John A CurtinBoris C Bastian
Apr 11, 2006·Trends in Biochemical Sciences·Leon O Murphy, John Blenis
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·James TsaiGideon Bollag
Jun 19, 2008·Cancer Research·Clara MontagutJeffrey Settleman
Sep 16, 2008·Molecular Cancer Therapeutics·Keiran S M SmalleyKatherine L Nathanson
Mar 3, 2009·Proceedings of the National Academy of Sciences of the United States of America·Christine A PratilasNeal Rosen
Sep 4, 2009·The New England Journal of Medicine·Charles M RudinJennifer A Low
Nov 17, 2009·Proceedings of the National Academy of Sciences of the United States of America·Caroline M EmeryLevi A Garraway
Dec 24, 2009·Molecular Systems Biology·Marcel SchillingUrsula Klingmüller
Apr 22, 2010·Journal of Translational Medicine·Jonas N SøndergaardAntoni Ribas
Jun 12, 2010·Science Translational Medicine·Steven WhittakerRichard Marais
Sep 8, 2010·The New England Journal of Medicine·Keith T FlahertyPaul B Chapman
Dec 24, 2010·Science Signaling·Oliver E SturmWalter Kolch
Mar 9, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nikhil WagleLevi A Garraway
Jun 7, 2011·The New England Journal of Medicine·Paul B ChapmanUNKNOWN BRIM-3 Study Group
Nov 10, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick A OberholzerLevi A Garraway
Dec 20, 2011·Biochemical and Biophysical Research Communications·Robert Roskoski
Jan 14, 2012·Expert Opinion on Therapeutic Targets·Libero SantarpiaAdel K El-Naggar
Jan 20, 2012·The New England Journal of Medicine·Fei SuRichard Marais
Jun 6, 2012·The New England Journal of Medicine·Keith T FlahertyUNKNOWN METRIC Study Group

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Citations

Dec 17, 2015·Journal of Neuropathology and Experimental Neurology·Jantima TanboonDavid N Louis
Mar 3, 2015·International Journal of Clinical Practice·R SousaS Papa
Feb 19, 2015·Archives of Toxicology·Eun Kyung Kim, Eui-Ju Choi
May 8, 2015·Nature Medicine·Stephen E GouldFrederic J de Sauvage
Apr 22, 2017·European Journal of Medicinal Chemistry·Mahesh R KulkarniShivaji S Pandit
May 27, 2014·American Society of Clinical Oncology Educational Book·Mark W Kieran
Nov 5, 2017·Oncotarget·Merope GriffinSophia N Karagiannis
Jul 2, 2020·International Journal of Molecular Sciences·Anna M CzarneckaPiotr Rutkowski
Sep 7, 2017·The Journal of Antibiotics·Masatomi IijimaMasakatsu Shibasaki
Feb 19, 2016·Advanced Healthcare Materials·Yu MiMauro Ferrari
Jun 28, 2019·Therapeutic Advances in Medical Oncology·Michel DucreuxMaximiliano Gelli
Oct 27, 2014·Oncotarget·Francesco SpagnoloPaola Queirolo

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