Stamping out RAF and MEK1/2 to inhibit the ERK1/2 pathway: an emerging threat to anticancer therapy

Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma

(2015) Maria Romina Girotti et al.   CANCER CELL

Regulation of RAF protein kinases in ERK signalling

(2015) Hugo Lavoie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Potential Therapeutic Strategies to Overcome Acquired Resistance to BRAF or MEK Inhibitors in BRAF Mutant Cancers

(2015) Ryan B. Corcoran et al.   Oncotarget

Intrinsic and acquired resistance to MEK1/2 inhibitors in cancer

(2014) Matthew J. Sale et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Disruption of CRAF-Mediated MEK Activation Is Required for Effective MEK Inhibition in KRAS Mutant Tumors

(2014) Piro Lito et al.   CANCER CELL

Abstract 2337: Efficacy of the RAF/PI3Kα/anti-EGFR triple combination LGX818 + BYL719 + cetuximab in BRAFV600Ecolorectal tumor models.

(2014) Giordano Caponigro et al.   CANCER RESEARCH

BRAF Inhibitor Resistance Mechanisms in Metastatic Melanoma: Spectrum and Clinical Impact

(2014) H. Rizos et al.   CLINICAL CANCER RESEARCH

Dabrafenib and Trametinib, Alone and in Combination for BRAF-Mutant Metastatic Melanoma

(2014) A. M. Menzies et al.   CLINICAL CANCER RESEARCH

Phase I study of XL281 (BMS-908662), a potent oral RAF kinase inhibitor, in patients with advanced solid tumors

(2014) Mark A. Dickson et al.   INVESTIGATIONAL NEW DRUGS

Novel ATP-Competitive MEK Inhibitor E6201 Is Effective against Vemurafenib-Resistant Melanoma Harboring the MEK1-C121S Mutation in a Preclinical Model

(2014) Y. Narita et al.   MOLECULAR CANCER THERAPEUTICS

The clinical development of MEK inhibitors

(2014) Yujie Zhao et al.   Nature Reviews Clinical Oncology

Rasfonin, a novel 2-pyrone derivative, induces ras-mutated Panc-1 pancreatic tumor cell death in nude mice

(2014) Z Xiao et al.   Cell Death & Disease

Phase I and pharmacokinetic/pharmacodynamic study of RO5126766, a first-in-class dual Raf/MEK inhibitor, in Japanese patients with advanced solid tumors

(2013) Kazunori Honda et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

A phase I dose-finding, safety and tolerability study of AZD8330 in patients with advanced malignancies

(2013) Roger B. Cohen et al.   EUROPEAN JOURNAL OF CANCER

Antitumor activity of pimasertib, a selective MEK 1/2 inhibitor, in combination with PI3K/mTOR inhibitors or with multi-targeted kinase inhibitors in pimasertib-resistant human lung and colorectal cancer cells

(2013) Erika Martinelli et al.   INTERNATIONAL JOURNAL OF CANCER

Pharmacodynamic Effects and Mechanisms of Resistance to Vemurafenib in Patients With Metastatic Melanoma

(2013) Kerstin Trunzer et al.   JOURNAL OF CLINICAL ONCOLOGY

MEK and the inhibitors: from bench to bedside

(2013) Akintunde Akinleye et al.   Journal of Hematology & Oncology

B-Raf and the inhibitors: from bench to bedside

(2013) Tiangui Huang et al.   Journal of Hematology & Oncology

MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study

(2013) Paolo A Ascierto et al.   LANCET ONCOLOGY

pERK 1/2 inhibit Caspase-8 induced apoptosis in cancer cells by phosphorylating it in a cell cycle specific manner

(2013) Ranadip Mandal et al.   Molecular Oncology

Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

(2013) Gunther Zimmermann et al.   NATURE

Mechanism of MEK inhibition determines efficacy in mutant KRAS- versus BRAF-driven cancers

(2013) Georgia Hatzivassiliou et al.   NATURE

Drug for an 'undruggable' protein

(2013) Nicole M. Baker et al.   NATURE

BRAF inhibitors in cancer therapy

(2013) Carolina Hertzman Johansson et al.   PHARMACOLOGY & THERAPEUTICS

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

(2013) H. J. Hocker et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

MEK inhibitors as a chemotherapeutic intervention in multiple myeloma

(2013) C Chang-Yew Leow et al.   Blood Cancer Journal

Concurrent MEK2 Mutation and BRAF Amplification Confer Resistance to BRAF and MEK Inhibitors in Melanoma

(2013) Jessie Villanueva et al.   Cell Reports

Tumour cell responses to MEK1/2 inhibitors: acquired resistance and pathway remodelling

(2012) Annette S. Little et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Abstract 3790: Preclinical profile of LGX818: A potent and selective RAF kinase inhibitor

(2012) Darrin D. Stuart et al.   CANCER RESEARCH

Abstract 3739: TAK-733, an investigational, selective MEK1/2 inhibitor, in combination with alisertib (MLN8237), an investigational, selective Aurora A kinase inhibitor is tolerated and results in additive to synergistic antitumor activity: Results from In Vivo Studies

(2012) Robyn Fabrey et al.   CANCER RESEARCH

Abstract 3738: A rationale for combining the targeted investigational agents TAK-733, a MEK1/2 inhibitor, with alisertib (MLN8237), an Aurora A kinase inhibitor, for cancer therapy

(2012) Sabrina Collins et al.   CANCER RESEARCH

Receptor tyrosine kinases in cancer escape from BRAF inhibitors

(2012) Roger S Lo   CELL RESEARCH

Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the MEK Inhibitor RO4987655 (CH4987655) in Patients with Advanced Solid Tumors

(2012) S. Leijen et al.   CLINICAL CANCER RESEARCH

RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors

(2012) Y. Su et al.   CLINICAL CANCER RESEARCH

First-in-Human, Phase I Dose-Escalation Study of the Safety, Pharmacokinetics, and Pharmacodynamics of RO5126766, a First-in-Class Dual MEK/RAF Inhibitor in Patients with Solid Tumors

(2012) M. Martinez-Garcia et al.   CLINICAL CANCER RESEARCH

358 A Multi-arm Phase 1 Dose Escalation Study of Safety, Pharmacokinetics, and Pharmacodynamics of the Dual PI3K/mTOR Inhibitors PF-04691502 (oral) and PF-05212384 (IV) in Combination with the MEK Inhibitor PD-0325901 or Irinotecan in Patients with Advanced Cancer

(2012) C. Britten et al.   EUROPEAN JOURNAL OF CANCER

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

(2012) Ravid Straussman et al.   NATURE

Vemurafenib: the first drug approved for BRAF-mutant cancer

(2012) Gideon Bollag et al.   NATURE REVIEWS DRUG DISCOVERY

Mechanisms of acquired resistance to ERK1/2 pathway inhibitors

(2012) A S Little et al.   ONCOGENE

Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

(2012) T. Maurer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mutant BRAF Melanomas—Dependence and Resistance

(2011) Poulikos I. Poulikakos et al.   CANCER CELL

Resistance to BRAF Inhibitors: Unraveling Mechanisms and Future Treatment Options

(2011) J. Villanueva et al.   CANCER RESEARCH

Vemurafenib and BRAF Inhibition: A New Class of Treatment for Metastatic Melanoma

(2011) J. J. Luke et al.   CLINICAL CANCER RESEARCH

Phase II, Open-Label, Randomized Trial of the MEK1/2 Inhibitor Selumetinib as Monotherapy versus Temozolomide in Patients with Advanced Melanoma

(2011) J. M. Kirkwood et al.   CLINICAL CANCER RESEARCH

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained In Vivo Pathway Inhibition

(2011) A. G. Gilmartin et al.   CLINICAL CANCER RESEARCH

Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling

(2011) Nikhil Wagle et al.   JOURNAL OF CLINICAL ONCOLOGY

Future perspectives in melanoma research. Meeting report from the "Melanoma Research: a bridge Naples-USA. Naples, December 6th-7 th2010"

(2011) Paolo A Ascierto et al.   Journal of Translational Medicine

Activation and Function of the MAPKs and Their Substrates, the MAPK-Activated Protein Kinases

(2011) M. Cargnello et al.   MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS

BRAFV600E: Implications for Carcinogenesis and Molecular Therapy

(2011) E. R. Cantwell-Dorris et al.   MOLECULAR CANCER THERAPEUTICS

Comprehensive Predictive Biomarker Analysis for MEK Inhibitor GSK1120212

(2011) J. Jing et al.   MOLECULAR CANCER THERAPEUTICS

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

(2011) Poulikos I. Poulikakos et al.   NATURE

Amplification of the Driving Oncogene, KRAS or BRAF, Underpins Acquired Resistance to MEK1/2 Inhibitors in Colorectal Cancer Cells

(2011) A. S. Little et al.   Science Signaling

Functional and molecular interactions between ERK and CHK2 in diffuse large B-cell lymphoma

(2011) Bojie Dai et al.   Nature Communications

The Raf Inhibitor Paradox: Unexpected Consequences of Targeted Drugs

(2010) Adrienne D. Cox et al.   CANCER CELL

RG7204 (PLX4032), a Selective BRAFV600E Inhibitor, Displays Potent Antitumor Activity in Preclinical Melanoma Models

(2010) H. Yang et al.   CANCER RESEARCH

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

(2010) Sonja J. Heidorn et al.   CELL

Phase II Clinical Trial of Sorafenib in Metastatic Medullary Thyroid Cancer

(2010) Elaine T. Lam et al.   JOURNAL OF CLINICAL ONCOLOGY

From basic research to clinical development of MEK1/2 inhibitors for cancer therapy

(2010) Christophe Frémin et al.   Journal of Hematology & Oncology

Identification of Predictive Markers of Response to the MEK1/2 Inhibitor Selumetinib (AZD6244) in K-ras-Mutated Colorectal Cancer

(2010) J. J. Tentler et al.   MOLECULAR CANCER THERAPEUTICS

RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

(2010) Poulikos I. Poulikakos et al.   NATURE

RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

(2010) Georgia Hatzivassiliou et al.   NATURE

COT drives resistance to RAF inhibition through MAP kinase pathway reactivation

(2010) Cory M. Johannessen et al.   NATURE

BRAF Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation

(2010) R. B. Corcoran et al.   Science Signaling

Antitumor Efficacy of the Novel RAF Inhibitor GDC-0879 Is Predicted by BRAFV600E Mutational Status and Sustained Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Pathway Suppression

(2009) K. P. Hoeflich et al.   CANCER RESEARCH

ERK-1 MAP kinase prevents TNF-induced apoptosis through bad phosphorylation and inhibition of Bax translocation in HeLa Cells

(2009) Bruna Pucci et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

MAPK signaling pathways in the regulation of hematopoiesis

(2009) Christian R. Geest et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Impact of Feedback Phosphorylation and Raf Heterodimerization on Normal and Mutant B-Raf Signaling

(2009) D. A. Ritt et al.   MOLECULAR AND CELLULAR BIOLOGY

KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer

(2009) J. J. Yeh et al.   MOLECULAR CANCER THERAPEUTICS

Negative Regulation of the EGFR-MAPK Cascade by Actin-MAL-Mediated Mig6/Errfi-1 Induction

(2009) Arnaud Descot et al.   MOLECULAR CELL

MEK1 mutations confer resistance to MEK and B-RAF inhibition

(2009) C. M. Emery et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

(2008) B. B. Friday et al.   CLINICAL CANCER RESEARCH

The regulation of extracellular signal-regulated kinase (ERK) in mammalian cells

(2008) Joe W. Ramos   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral, Small-Molecule Mitogen-Activated Protein Kinase Kinase 1/2 Inhibitor AZD6244 (ARRY-142886) in Patients With Advanced Cancers

(2008) Alex A. Adjei et al.   JOURNAL OF CLINICAL ONCOLOGY

Adaptor SKAP-55 Binds p21ras Activating Exchange Factor RasGRP1 and Negatively Regulates the p21ras-ERK Pathway in T-Cells

(2008) Helga Schneider et al.   PLoS One

Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity

(2008) J. Tsai et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA