The RAF-MEK-ERK pathway: targeting ERK to overcome obstacles to effective cancer therapy

Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine inhibitors of Erk2

(2014) James F. Blake et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Cancer statistics, 2014

(2014) Rebecca Siegel et al.   CA-A CANCER JOURNAL FOR CLINICIANS

Wild-Type H- and N-Ras Promote Mutant K-Ras-Driven Tumorigenesis by Modulating the DNA Damage Response

(2014) Elda Grabocka et al.   CANCER CELL

Prospects for MEK inhibitors for treating cancer

(2014) Juan Martin-Liberal et al.   Expert Opinion On Drug Safety

Differential activity of MEK and ERK inhibitors in BRAF inhibitor resistant melanoma

(2014) Matteo S. Carlino et al.   Molecular Oncology

Oncogene Mimicry as a Mechanism of Primary Resistance to BRAF Inhibitors

(2014) Martin L. Sos et al.   Cell Reports

Extracellular signal-regulated kinase-5: Novel mediator of insulin and tumor necrosis factor α-stimulated vascular cell adhesion molecule-1 expression in vascular cells 细胞外信号调节激酶-5：一种新的调节胰岛素与肿瘤坏死因子α刺激下的血管细胞上的血管细胞粘附分子-1表达的介质

(2014) Daniel Z. Mackesy et al.   Journal of Diabetes

Kinase Drug Discovery – What’s Next in the Field?

(2013) Philip Cohen et al.   ACS Chemical Biology

Inhibitors of protein kinases

(2013) David Shugar et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

Inhibition of both BRAF and MEK in BRAFV600E mutant melanoma restores compromised dendritic cell (DC) function while having differential direct effects on DC properties

(2013) Patrick A. Ott et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

In Vivo MAPK Reporting Reveals the Heterogeneity in Tumoral Selection of Resistance to RAF Inhibitors

(2013) K. J. Basile et al.   CANCER RESEARCH

RSK Isoforms in Cancer Cell Invasion and Metastasis

(2013) F. J. Sulzmaier et al.   CANCER RESEARCH

ERK1/2 Blockade Prevents Epithelial-Mesenchymal Transition in Lung Cancer Cells and Promotes Their Sensitivity to EGFR Inhibition

(2013) J. M. Buonato et al.   CANCER RESEARCH

C-RAF Mutations Confer Resistance to RAF Inhibitors

(2013) R. Antony et al.   CANCER RESEARCH

Development, Characterization, and Reversal of Acquired Resistance to the MEK1 Inhibitor Selumetinib (AZD6244) in an In Vivo Model of Childhood Astrocytoma

(2013) H. K. Bid et al.   CLINICAL CANCER RESEARCH

Synergistic inhibition of ovarian cancer cell growth by combining selective PI3K/mTOR and RAS/ERK pathway inhibitors

(2013) Karen E. Sheppard et al.   EUROPEAN JOURNAL OF CANCER

Resistance to BRAF-targeted therapy in melanoma

(2013) Ryan J. Sullivan et al.   EUROPEAN JOURNAL OF CANCER

B-Raf mutation: A key player in molecular biology of cancer

(2013) M.A. Rahman et al.   EXPERIMENTAL AND MOLECULAR PATHOLOGY

Requirement of B-Raf, C-Raf, and A-Raf for the growth and survival of mouse embryonic stem cells

(2013) Wenjing Guo et al.   EXPERIMENTAL CELL RESEARCH

p38-Mediated phosphorylation of Eps15 endocytic adaptor protein

(2013) Yue Zhou et al.   FEBS LETTERS

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

Mitogen-Activated Protein (MAP) Kinase Scaffolding Proteins: A Recount

(2013) Melanie Meister et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ERK2 but not ERK1 mediates HGF-induced motility in non-small cell lung carcinoma cell lines

(2013) S. Radtke et al.   JOURNAL OF CELL SCIENCE

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

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

B-Raf and the inhibitors: from bench to bedside

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

Melanoma combination therapies ward off tumor resistance

(2013) Ken Garber   NATURE BIOTECHNOLOGY

IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase–driven tumors

(2013) Katherine L Jameson et al.   NATURE MEDICINE

Targeting RAF-MEK-ERK kinase-scaffold interactions in cancer

(2013) Darrin D Stuart et al.   NATURE MEDICINE

Ipilimumab, Vemurafenib, Dabrafenib, and Trametinib: Synergistic Competitors in the Clinical Management of BRAF Mutant Malignant Melanoma

(2013) J. J. Luke et al.   ONCOLOGIST

MEK in cancer and cancer therapy

(2013) Cindy Neuzillet et al.   PHARMACOLOGY & THERAPEUTICS

ERK5 Activation by Gq-Coupled Muscarinic Receptors Is Independent of Receptor Internalization and β-Arrestin Recruitment

(2013) Guzmán Sánchez-Fernández et al.   PLoS One

Paradoxical activation and RAF inhibitor resistance of BRAF protein kinase fusions characterizing pediatric astrocytomas

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

ERK Pathway Inhibitors: How Low Should We Go?

(2013) M. H. Nissan et al.   Cancer Discovery

A Genome-Scale RNA Interference Screen Implicates NF1 Loss in Resistance to RAF Inhibition

(2013) Steven R. Whittaker et al.   Cancer Discovery

Frequent Mutation of the PI3K Pathway in Head and Neck Cancer Defines Predictive Biomarkers

(2013) V. W. Y. Lui et al.   Cancer Discovery

MAP Kinase Pathway Alterations in BRAF-Mutant Melanoma Patients with Acquired Resistance to Combined RAF/MEK Inhibition

(2013) N. Wagle et al.   Cancer Discovery

Discovery of a Novel ERK Inhibitor with Activity in Models of Acquired Resistance to BRAF and MEK Inhibitors

(2013) E. J. Morris et al.   Cancer Discovery

The Genetic Landscape of Clinical Resistance to RAF Inhibition in Metastatic Melanoma

(2013) E. M. Van Allen et al.   Cancer Discovery

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

(2013) Jessie Villanueva et al.   Cell Reports

Relief of Profound Feedback Inhibition of Mitogenic Signaling by RAF Inhibitors Attenuates Their Activity in BRAFV600E Melanomas

(2012) Piro Lito et al.   CANCER CELL

MAPK signaling in cisplatin-induced death: predominant role of ERK1 over ERK2 in human hepatocellular carcinoma cells

(2012) Jean-Philippe Guégan et al.   CARCINOGENESIS

Discovery of Potent and Selective Covalent Inhibitors of JNK

(2012) Tinghu Zhang et al.   CHEMISTRY & BIOLOGY

Bridging the Gap between Preclinical and Clinical Studies Using Pharmacokinetic-Pharmacodynamic Modeling: An Analysis of GDC-0973, a MEK Inhibitor

(2012) H. Wong et al.   CLINICAL CANCER RESEARCH

Whole-Genome Sequencing in Personalized Therapeutics

(2012) P Cordero et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

MAP kinase signalling cascades and transcriptional regulation

(2012) Shen-Hsi Yang et al.   GENE

RAF265, a dual BRAF and VEGFR2 inhibitor, prevents osteoclast formation and resorption. Therapeutic implications

(2012) Antonio Garcia-Gomez et al.   INVESTIGATIONAL NEW DRUGS

Phase II Study of the MEK1/MEK2 Inhibitor Trametinib in Patients With MetastaticBRAF-Mutant Cutaneous Melanoma Previously Treated With or Without a BRAF Inhibitor

(2012) Kevin B. Kim et al.   JOURNAL OF CLINICAL ONCOLOGY

Specifically targeting ERK1 or ERK2 kills Melanoma cells

(2012) Jianzhong Qin et al.   Journal of Translational Medicine

Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial

(2012) Gerald S Falchook et al.   LANCET

Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial

(2012) Axel Hauschild et al.   LANCET

Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial

(2012) Jeffrey R Infante et al.   LANCET ONCOLOGY

Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial

(2012) Georgina V Long et al.   LANCET ONCOLOGY

Personalized oncology: Recent advances and future challenges

(2012) Madhu Kalia   METABOLISM-CLINICAL AND EXPERIMENTAL

ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors

(2012) G. Hatzivassiliou et al.   MOLECULAR CANCER THERAPEUTICS

Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma

(2012) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

ERK1/2 MAP kinases: Structure, function, and regulation

(2012) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Mammalian MAPK Signal Transduction Pathways Activated by Stress and Inflammation: A 10-Year Update

(2012) John M. Kyriakis et al.   PHYSIOLOGICAL REVIEWS

A rare point mutation in the Ras oncogene in hepatocellular carcinoma

(2012) Akinobu Taketomi et al.   SURGERY TODAY

Approaches to discover non-ATP site kinase inhibitors

(2012) Lori Krim Gavrin et al.   MedChemComm

Melanoma whole-exome sequencing identifies V600E B-RAF amplification-mediated acquired B-RAF inhibitor resistance

(2012) Hubing Shi et al.   Nature Communications

DUSPs, to MAP kinases and beyond

(2012) Ching-Yu Huang et al.   Cell and Bioscience

MEK1/2 dual-specificity protein kinases: Structure and regulation

(2011) Robert Roskoski   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

(2011) J. Li et al.   CANCER RESEARCH

Resistance to Selective BRAF Inhibition Can Be Mediated by Modest Upstream Pathway Activation

(2011) F. Su et al.   CANCER RESEARCH

Identification of the MEK1(F129L) Activating Mutation as a Potential Mechanism of Acquired Resistance to MEK Inhibition in Human Cancers Carrying the B-RafV600E Mutation

(2011) H. Wang et al.   CANCER RESEARCH

Hallmarks of Cancer: The Next Generation

(2011) Douglas Hanahan et al.   CELL

Total ERK1/2 activity regulates cell proliferation

(2011) Renaud Lefloch et al.   CELL CYCLE

Signal control through Raf: in sickness and in health

(2011) Jihan K Osborne et al.   CELL RESEARCH

MAPK pathway activation in pilocytic astrocytoma

(2011) David T. W. Jones et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

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

Challenges ahead in signal transduction: MAPK as an example

(2011) Christina Kiel et al.   CURRENT OPINION IN BIOTECHNOLOGY

A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy

(2011) György Bodoky et al.   INVESTIGATIONAL NEW DRUGS

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

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

Phase II Study of the Mitogen-Activated Protein Kinase 1/2 Inhibitor Selumetinib in Patients With Advanced Hepatocellular Carcinoma

(2011) Bert H. O'Neil et al.   JOURNAL OF CLINICAL ONCOLOGY

Strong negative feedback from Erk to Raf confers robustness to MAPK signalling

(2011) R. Fritsche-Guenther et al.   Molecular Systems Biology

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

(2011) Poulikos I. Poulikakos et al.   NATURE

Resistance to BRAF Inhibition in Melanomas

(2011) David B. Solit et al.   NEW ENGLAND JOURNAL OF MEDICINE

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

(2011) Paul B. Chapman et al.   NEW ENGLAND JOURNAL OF MEDICINE

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

Resistance to MEK Inhibitors: Should We Co-Target Upstream?

(2011) P. I. Poulikakos et al.   Science Signaling

Preexistence and Clonal Selection of MET Amplification in EGFR Mutant NSCLC

(2010) Alexa B. Turke et al.   CANCER CELL

Small-Molecule Inhibitors of the ERK Signaling Pathway: Towards Novel Anticancer Therapeutics

(2010) Jeremy L. Yap et al.   ChemMedChem

A Phase II Study of PD-0325901, an Oral MEK Inhibitor, in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer

(2010) E. B. Haura et al.   CLINICAL CANCER RESEARCH

Phase I Pharmacokinetic and Pharmacodynamic Study of the Oral MAPK/ERK Kinase Inhibitor PD-0325901 in Patients with Advanced Cancers

(2010) P. M. LoRusso et al.   CLINICAL CANCER RESEARCH

Emerging MEK inhibitors

(2010) James A McCubrey et al.   EXPERT OPINION ON EMERGING DRUGS

A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens

(2010) Jaafar Bennouna et al.   INVESTIGATIONAL NEW DRUGS

A Phase II, Open-Label, Randomized Study to Assess the Efficacy and Safety of AZD6244 (ARRY-142886) Versus Pemetrexed in Patients with Non-small Cell Lung Cancer Who Have Failed One or Two Prior Chemotherapeutic Regimens

(2010) John D. Hainsworth et al.   Journal of Thoracic Oncology

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

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation

(2010) Ramin Nazarian et al.   NATURE

Inhibition of Mutated, Activated BRAF in Metastatic Melanoma

(2010) Keith T. Flaherty et al.   NEW ENGLAND JOURNAL OF MEDICINE

Positioning of a Molecular-Targeted Agent, Sorafenib, in the Treatment Algorithm for Hepatocellular Carcinoma and Implication of Many Complete Remission Cases in Japan

(2010) Masatoshi Kudo et al.   ONCOLOGY

The RAF inhibitor PLX4032 inhibits ERK signaling and tumor cell proliferation in a V600E BRAF-selective manner

(2010) E. W. Joseph et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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

Intrinsic resistance to the MEK1/2 inhibitor AZD6244 (ARRY-142886) is associated with weak ERK1/2 signalling and/or strong PI3K signalling in colorectal cancer cell lines

(2009) Kathryn Balmanno et al.   INTERNATIONAL JOURNAL OF CANCER

Positive- and negative-feedback regulations coordinate the dynamic behavior of the Ras-Raf-MEK-ERK signal transduction pathway

(2009) S.-Y. Shin et al.   JOURNAL OF CELL SCIENCE

Results of a Phase III, Randomized, Placebo-Controlled Study of Sorafenib in Combination With Carboplatin and Paclitaxel As Second-Line Treatment in Patients With Unresectable Stage III or Stage IV Melanoma

(2009) Axel Hauschild et al.   JOURNAL OF CLINICAL ONCOLOGY

Structure-Guided Design of Potent and Selective Pyrimidylpyrrole Inhibitors of Extracellular Signal-Regulated Kinase (ERK) Using Conformational Control

(2009) Alex M. Aronov et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

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

Tumour cell survival signalling by the ERK1/2 pathway

(2008) K Balmanno et al.   CELL DEATH AND DIFFERENTIATION

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

The N-Terminal Domain of ERK1 Accounts for the Functional Differences with ERK2

(2008) Matilde Marchi et al.   PLoS One