MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus

Integrated molecular and clinical analysis of low-grade gliomas in children with neurofibromatosis type 1 (NF1)

(2021) Michael J. Fisher et al.   ACTA NEUROPATHOLOGICA

NF106: A Neurofibromatosis Clinical Trials Consortium Phase II Trial of the MEK Inhibitor Mirdametinib (PD-0325901) in Adolescents and Adults With NF1-Related Plexiform Neurofibromas

(2021) Brian D. Weiss et al.   JOURNAL OF CLINICAL ONCOLOGY

Treatment during a developmental window prevents NF1-associated optic pathway gliomas by targeting Erk-dependent migrating glial progenitors

(2021) Emmanuelle S. Jecrois et al.   DEVELOPMENTAL CELL

Impact of MEK Inhibitor Therapy on Neurocognitive Functioning in NF1

(2021) Karin S. Walsh et al.   Neurology-Genetics

Implications of New Understandings of Gliomas in Children and Adults with NF1: Report of a Consensus Conference

(2020) Roger J Packer et al.   NEURO-ONCOLOGY

Phase II trial of the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886 Hydrogen Sulfate) in adults with neurofibromatosis type 1 (NF1) and inoperable plexiform neurofibromas (PN).

(2020) Geraldine Helen O'Sullivan Coyne et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase II study of oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1-associated pediatric low-grade glioma A phase II study of continuous oral mTOR inhibitor everolimus for recurrent, radiographic-progressive neurofibromatosis type 1–associated pediatric low-grade glioma: a Neurofibromatosis Clinical Trials Consortium study

(2020) Nicole J Ullrich et al.   NEURO-ONCOLOGY

Selumetinib in Children with Inoperable Plexiform Neurofibromas

(2020) Andrea M. Gross et al.   NEW ENGLAND JOURNAL OF MEDICINE

The Use of MEK Inhibitors in Neurofibromatosis Type 1–Associated Tumors and Management of Toxicities

(2020) Laura J. Klesse et al.   ONCOLOGIST

Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy

(2020) Daniel Baumann et al.   Nature Communications

A molecular basis for neurofibroma-associated skeletal manifestations in NF1

(2020) Yun Ma et al.   GENETICS IN MEDICINE

Trametinib-associated Hyponatremia in a Child With Low-grade Glioma is Not Seen Following Treatment With Alternative MEK Inhibitor

(2020) Margot A. Lazow et al.   JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY

Humanized neurofibroma model from induced pluripotent stem cells delineates tumor pathogenesis and developmental origins

(2020) Juan Mo et al.   JOURNAL OF CLINICAL INVESTIGATION

NFB-17. MEK INHIBITOR BINIMETINIB SHOWS CLINICAL ACTIVITY IN CHILDREN WITH NEUROFIBROMATOSIS TYPE 1- ASSOCIATED PLEXIFORM NEUROFIBROMAS: A REPORT FROM PNOC AND THE NF CLINICAL TRIALS CONSORTIUM

(2020) Sabine Mueller et al.   NEURO-ONCOLOGY

OCULAR ADVERSE EVENTS ASSOCIATED WITH MEK INHIBITORS

(2019) Silvia Méndez-Martínez et al.   RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES

Cutaneous reactions to targeted therapies in children with CNS tumors: A cross-sectional study

(2019) Hannah Song et al.   PEDIATRIC BLOOD & CANCER

Substantial pain burden in frequency, intensity, interference and chronicity among children and adults with neurofibromatosis Type 1

(2019) Alanna M. Kongkriangkai et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART A

Cdkn2a (Arf) loss drives NF1-associated atypical neurofibroma and malignant transformation

(2019) Steven D Rhodes et al.   HUMAN MOLECULAR GENETICS

Hypertrophic Cardiomyopathy in Noonan Syndrome Treated by MEK-Inhibition

(2019) Gregor Andelfinger et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Selumetinib in paediatric patients with BRAF-aberrant or neurofibromatosis type 1-associated recurrent, refractory, or progressive low-grade glioma: a multicentre, phase 2 trial

(2019) Jason Fangusaro et al.   LANCET ONCOLOGY

Encorafenib, Binimetinib, and Cetuximab in BRAF V600E–Mutated Colorectal Cancer

(2019) Scott Kopetz et al.   NEW ENGLAND JOURNAL OF MEDICINE

Cognition, ADHD Symptoms, and Functional Impairment in Children and Adolescents With Neurofibromatosis Type 1

(2019) Jonathan M. Payne et al.   Journal of Attention Disorders

Mutant BRAF and MEK Inhibitors Regulate the Tumor Immune Microenvironment via Pyroptosis

(2019) Dan A. Erkes et al.   Cancer Discovery

Genomic status of MET potentiates sensitivity to MET and MEK inhibition in NF1-related malignant peripheral nerve sheath tumors

(2018) Jacqueline D Peacock et al.   CANCER RESEARCH

Height Growth Impairment in Children With Neurofibromatosis Type 1 Is Characterized by Decreased Pubertal Growth Velocity in Both Sexes

(2018) Nicholas R. Zessis et al.   JOURNAL OF CHILD NEUROLOGY

LGG-01. EVALUATION OF COBIMETINIB, A MEK INHIBITOR, IN LOW-GRADE PEDIATRIC BRAIN TUMORS

(2018) Martin Roskoski et al.   NEURO-ONCOLOGY

LGG-44. A PHASE I DOSE ESCALATION TRIAL OF THE MEK1/2 INHIBITOR MEK162 (BINIMETINIB) IN CHILDREN WITH LOW-GRADE GLIOMAS AND OTHER RAS/RAF PATHWAY-ACTIVATED TUMORS

(2018) Nathan Robison et al.   NEURO-ONCOLOGY

LTBK-01. UPDATES ON THE PHASE II AND RE-TREATMENT STUDY OF AZD6244 (SELUMETINIB) FOR CHILDREN WITH RECURRENT OR REFRACTORY PEDIATRIC LOW GRADE GLIOMA: A PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC) STUDY

(2018) Jason R Fangusaro et al.   NEURO-ONCOLOGY

Trametinib in pediatric patients with neurofibromatosis type 1 (NF-1)–associated plexiform neurofibroma: A phase I/IIa study.

(2018) Geoffrey Brian McCowage et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase 1 trial of trametinib alone and in combination with dabrafenib in children and adolescents with relapsed solid tumors or neurofibromatosis type 1 (NF1) progressive plexiform neurofibromas (PN).

(2018) Birgit Geoerger et al.   JOURNAL OF CLINICAL ONCOLOGY

Osteopenia and fractures associated with long-term therapy with MEK inhibitors

(2018) Marc Dumas et al.   MELANOMA RESEARCH

The senescence-associated secretory phenotype mediates oncogene-induced senescence in pediatric pilocytic astrocytoma

(2018) Juliane L. Buhl et al.   CLINICAL CANCER RESEARCH

Cellular Origin, Tumor Progression, and Pathogenic Mechanisms of Cutaneous Neurofibromas Revealed by Mice with Nf1 Knockout in Boundary Cap Cells

(2018) Katarzyna J. Radomska et al.   Cancer Discovery

Spatiotemporal Loss of NF1 in Schwann Cell Lineage Leads to Different Types of Cutaneous Neurofibroma Susceptible to Modification by the Hippo Pathway

(2018) Zhiguo Chen et al.   Cancer Discovery

Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1—a consensus overview

(2017) Markku M. Miettinen et al.   HUMAN PATHOLOGY

The impact of P-glycoprotein and breast cancer resistance protein on the brain pharmacokinetics and pharmacodynamics of a panel of MEK inhibitors

(2017) Mark C. de Gooijer et al.   INTERNATIONAL JOURNAL OF CANCER

Prolonged Mek1/2 suppression impairs the developmental potential of embryonic stem cells

(2017) Jiho Choi et al.   NATURE

A phase I trial of the MEK inhibitor selumetinib (AZD6244) in pediatric patients with recurrent or refractory low-grade glioma: a Pediatric Brain Tumor Consortium (PBTC) study

(2017) Anuradha Banerjee et al.   NEURO-ONCOLOGY

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma

(2017) Georgina V. Long et al.   NEW ENGLAND JOURNAL OF MEDICINE

Moxibustion eases chronic inflammatory visceral pain through regulating MEK, ERK and CREB in rats

(2017) Zhi-Yuan Li et al.   WORLD JOURNAL OF GASTROENTEROLOGY

Mechanisms underlying cognitive deficits in a mouse model for Costello Syndrome are distinct from other RASopathy mouse models

(2017) Jadwiga Schreiber et al.   Scientific Reports

The MEK inhibitor selumetinib complements CTLA-4 blockade by reprogramming the tumor immune microenvironment

(2017) Edmund Poon et al.   Journal for ImmunoTherapy of Cancer

BRAF and MEK inhibitors in pediatric glioma: new therapeutic strategies, new toxicities

(2016) Daniela Rizzo et al.   Expert Opinion on Drug Metabolism & Toxicology

A first-in-human phase I study to evaluate the MEK1/2 inhibitor, cobimetinib, administered daily in patients with advanced solid tumors

(2016) Lee S. Rosen et al.   INVESTIGATIONAL NEW DRUGS

Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers

(2016) Rebecca Lock et al.   JOURNAL OF CLINICAL INVESTIGATION

Cobimetinib combined with vemurafenib in advanced BRAFV600-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial

(2016) Paolo A Ascierto et al.   LANCET ONCOLOGY

Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials

(2016) Pamela L. Wolters et al.   NEUROLOGY

Activity of Selumetinib in Neurofibromatosis Type 1–Related Plexiform Neurofibromas

(2016) Eva Dombi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Establishment and application of a novel patient-derived KIAA1549:BRAF-driven pediatric pilocytic astrocytoma model for preclinical drug testing

(2016) Florian Selt et al.   Oncotarget

Trametinib-induced Left Ventricular Dysfunction in a Child With Relapsed Neuroblastoma

(2015) Shakeel Modak et al.   JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY

The genomic landscape of juvenile myelomonocytic leukemia

(2015) Elliot Stieglitz et al.   NATURE GENETICS

Co-targeting the MAPK and PI3K/AKT/mTOR pathways in two genetically engineered mouse models of schwann cell tumors reduces tumor grade and multiplicity

(2015) Adrienne L. Watson et al.   Oncotarget

Combined MEK and JAK inhibition abrogates murine myeloproliferative neoplasm

(2014) Guangyao Kong et al.   JOURNAL OF CLINICAL INVESTIGATION

Role of P-Glycoprotein on the Brain Penetration and Brain Pharmacodynamic Activity of the MEK Inhibitor Cobimetinib

(2014) Edna F. Choo et al.   MOLECULAR PHARMACEUTICS

PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies

(2014) Thomas De Raedt et al.   NATURE

Asfotase-α improves bone growth, mineralization and strength in mouse models of neurofibromatosis type-1

(2014) Jean de la Croix Ndong et al.   NATURE MEDICINE

Mechanism and treatment for learning and memory deficits in mouse models of Noonan syndrome

(2014) Yong-Seok Lee et al.   NATURE NEUROSCIENCE

Akt- or MEK-mediated mTOR inhibition suppresses Nf1 optic glioma growth

(2014) Aparna Kaul et al.   NEURO-ONCOLOGY

Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a Neurofibromatosis Clinical Trials Consortium phase II study

(2014) B. Weiss et al.   NEURO-ONCOLOGY

Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

(2014) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Defining Key Signaling Nodes and Therapeutic Biomarkers in NF1-Mutant Cancers

(2014) C. F. Malone et al.   Cancer Discovery

Transient inhibition of the ERK pathway prevents cerebellar developmental defects and improves long-term motor functions in murine models of neurofibromatosis type 1

(2014) Edward Kim et al.   eLife

Transgenic Mice Overexpressing Neuregulin-1 Model Neurofibroma-Malignant Peripheral Nerve Sheath Tumor Progression and Implicate Specific Chromosomal Copy Number Variations in Tumorigenesis

(2013) Syed J. Kazmi et al.   AMERICAN JOURNAL OF PATHOLOGY

Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib)

(2013) J. El-Hoss et al.   BONE

Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation

(2013) Alice F. Goodwin et al.   HUMAN MOLECULAR GENETICS

Functional outcome measures for NF1-associated optic pathway glioma clinical trials

(2013) M. J. Fisher et al.   NEUROLOGY

Sirolimus for non-progressive NF1-associated plexiform neurofibromas: An NF clinical trials consortium phase II study

(2013) Brian Weiss et al.   PEDIATRIC BLOOD & CANCER

ERK Inhibition Rescues Defects in Fate Specification of Nf1-Deficient Neural Progenitors and Brain Abnormalities

(2012) Yuan Wang et al.   CELL

A controlled register-based study of 460 neurofibromatosis 1 patients: Increased fracture risk in children and adults over 41 years of age

(2012) Eetu Heervä et al.   JOURNAL OF BONE AND MINERAL RESEARCH

MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors

(2012) Walter J. Jessen et al.   JOURNAL OF CLINICAL INVESTIGATION

Visual outcomes in children with neurofibromatosis type 1-associated optic pathway glioma following chemotherapy: a multicenter retrospective analysis

(2012) M. J. Fisher et al.   NEURO-ONCOLOGY

18-fluorodeoxyglucose-positron emission tomography (FDG-PET) evaluation of nodular lesions in patients with neurofibromatosis type 1 and plexiform neurofibromas (PN) or malignant peripheral nerve sheath tumors (MPNST)

(2012) Holly Meany et al.   PEDIATRIC BLOOD & CANCER

Costello and cardio-facio-cutaneous syndromes: Moving toward clinical trials in RASopathies

(2011) Katherine A. Rauen et al.   AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS

Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors

(2011) Eline Beert et al.   GENES CHROMOSOMES & CANCER

Following nerve injury neuregulin-1 drives microglial proliferation and neuropathic pain via the MEK/ERK pathway

(2011) Margarita Calvo et al.   GLIA

A murine model of neurofibromatosis type 1 tibial pseudarthrosis featuring proliferative fibrous tissue and osteoclast-like cells

(2011) Jad El-Hoss et al.   JOURNAL OF BONE AND MINERAL RESEARCH

MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1L613V mutation

(2011) Xue Wu et al.   JOURNAL OF CLINICAL INVESTIGATION

Plexiform Neurofibromas in Children with Neurofibromatosis Type 1: Frequency and Associated Clinical Deficits

(2011) Rosa Nguyen et al.   JOURNAL OF PEDIATRICS

Mortality Associated with Neurofibromatosis 1: A Cohort Study of 1895 Patients in 1980-2006 in France

(2011) Tu Duong et al.   Orphanet Journal of Rare Diseases

Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder

(2011) Henry H. Lai et al.   PAIN

A MEK Inhibitor Abrogates Myeloproliferative Disease in Kras Mutant Mice

(2011) N. Lyubynska et al.   Science Translational Medicine

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

Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndrome–associated Sos1 mutation

(2010) Peng-Chieh Chen et al.   JOURNAL OF CLINICAL INVESTIGATION

Initial testing (stage 1) of AZD6244 (ARRY-142886) by the pediatric preclinical testing program

(2010) E. Anders Kolb et al.   PEDIATRIC BLOOD & CANCER

Noonan syndrome is associated with enhanced pERK activity, the repression of which can prevent craniofacial malformations

(2009) T. Nakamura et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA