Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives

Study design and rationale for a randomised, placebo-controlled, double-blind study to assess the efficacy of selumetinib (AZD6244; ARRY-142886) in combination with dacarbazine in patients with metastatic uveal melanoma (SUMIT)

(2015) Richard D. Carvajal et al.   BMC CANCER

Paracrine Effect of NRG1 and HGF Drives Resistance to MEK Inhibitors in Metastatic Uveal Melanoma

(2015) H. Cheng et al.   CANCER RESEARCH

Genomic Classification of Cutaneous Melanoma

(2015) Rehan Akbani et al.   CELL

Treatment of NRAS-Mutant Melanoma

(2015) Douglas B. Johnson et al.   CURRENT TREATMENT OPTIONS IN ONCOLOGY

Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial

(2015) Georgina V Long et al.   LANCET

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

(2015) Caroline Robert et al.   NEW ENGLAND JOURNAL OF MEDICINE

Phase II DeCOG-Study of Ipilimumab in Pretreated and Treatment-Naïve Patients with Metastatic Uveal Melanoma

(2015) Lisa Zimmer et al.   PLoS One

Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAF V600E melanoma

(2015) Siwen Hu-Lieskovan et al.   Science Translational Medicine

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

(2014) Piro Lito et al.   CANCER CELL

Mutant Gq/11 Promote Uveal Melanoma Tumorigenesis by Activating YAP

(2014) Fa-Xing Yu et al.   CANCER CELL

Hippo-Independent Activation of YAP by the GNAQ Uveal Melanoma Oncogene through a Trio-Regulated Rho GTPase Signaling Circuitry

(2014) Xiaodong Feng et al.   CANCER CELL

Effect of Selumetinib vs Chemotherapy on Progression-Free Survival in Uveal Melanoma

(2014) Richard D. Carvajal et al.   JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION

Abstract B75: A first in-human phase I study to evaluate the MEK1/2 inhibitor GDC-0623 in patients with advanced solid tumors.

(2014) A. El-Khoueiry et al.   MOLECULAR CANCER THERAPEUTICS

Overexpression of DDX43 Mediates MEK Inhibitor Resistance through RAS Upregulation in Uveal Melanoma Cells

(2014) G. Ambrosini et al.   MOLECULAR CANCER THERAPEUTICS

Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

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

Clinical activity of ipilimumab for metastatic uveal melanoma

(2013) Jason J. Luke et al.   CANCER

Enhanced Inhibition of ERK Signaling by a Novel Allosteric MEK Inhibitor, CH5126766, That Suppresses Feedback Reactivation of RAF Activity

(2013) Nobuya Ishii et al.   CANCER RESEARCH

Selumetinib plus dacarbazine versus placebo plus dacarbazine as first-line treatment for BRAF-mutant metastatic melanoma: a phase 2 double-blind randomised study

(2013) Caroline Robert et al.   LANCET 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

Inhibition of Mutant GNAQ Signaling in Uveal Melanoma Induces AMPK-Dependent Autophagic Cell Death

(2013) G. Ambrosini et al.   MOLECULAR CANCER THERAPEUTICS

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

(2013) Georgia Hatzivassiliou et al.   NATURE

Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance

(2013) Meghna Das Thakur et al.   NATURE

Tumor adaptation and resistance to RAF inhibitors

(2013) Piro Lito et al.   NATURE MEDICINE

Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutations

(2013) X Chen et al.   ONCOGENE

A prolonged complete response in a patient with BRAF-mutated melanoma stage IV treated with the MEK1/2 inhibitor selumetinib (AZD6244)

(2012) Marye J. Boers-Sonderen et al.   ANTI-CANCER DRUGS

The MEK1/2 inhibitor, selumetinib (AZD6244; ARRY-142886), enhances anti-tumour efficacy when combined with conventional chemotherapeutic agents in human tumour xenograft models

(2012) S V Holt et al.   BRITISH JOURNAL OF CANCER

Clinical responses to selumetinib (AZD6244; ARRY-142886)-based combination therapy stratified by gene mutations in patients with metastatic melanoma

(2012) Sapna P. Patel et al.   CANCER

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

(2012) Piro Lito et al.   CANCER CELL

Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ- and GNA11-Dependent Manner

(2012) J. S. Khalili 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

Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial

(2012) Gerald S Falchook et al.   LANCET ONCOLOGY

Abstract B243: A phase I dose-escalation study of MEK inhibitor MEK162 (ARRY-438162) in patients with advanced solid tumors.

(2012) J. C. Bendell 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

Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)

(2012) Kenneth D. Rice et al.   ACS Medicinal Chemistry Letters

Discovery of TAK-733, a potent and selective MEK allosteric site inhibitor for the treatment of cancer

(2011) Qing Dong et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

A phase I, open-label, randomized crossover study to assess the effect of dosing of the MEK 1/2 inhibitor Selumetinib (AZD6244; ARRY-142866) in the presence and absence of food in patients with advanced solid tumors

(2011) Suzanne Leijen et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Intermittent Administration of MEK Inhibitor GDC-0973 plus PI3K Inhibitor GDC-0941 Triggers Robust Apoptosis and Tumor Growth Inhibition

(2011) K. P. Hoeflich et al.   CANCER RESEARCH

Therapeutic Implications of the Emerging Molecular Biology of Uveal Melanoma

(2011) M. Patel 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

Uveal Melanoma: Trends in Incidence, Treatment, and Survival

(2011) Arun D. Singh et al.   OPHTHALMOLOGY

Pharmacokinetics and pharmacodynamics of AZD6244 (ARRY-142886) in tumor-bearing nude mice

(2010) Cathrine L. Denton et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

MEK1/2 Inhibitors AS703026 and AZD6244 May Be Potential Therapies forKRASMutated Colorectal Cancer That Is Resistant to EGFR Monoclonal Antibody Therapy

(2010) Juyong Yoon et al.   CANCER RESEARCH

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

The First-in-Human Study of the Hydrogen Sulfate (Hyd-Sulfate) Capsule of the MEK1/2 Inhibitor AZD6244 (ARRY-142886): A Phase I Open-Label Multicenter Trial in Patients with Advanced Cancer

(2010) U. Banerji et al.   CLINICAL CANCER RESEARCH

Evaluation of the mTOR pathway in ocular (uvea and conjunctiva) melanoma

(2010) Helena Pópulo et al.   MELANOMA RESEARCH

Mutations inGNA11in Uveal Melanoma

(2010) Catherine D. Van Raamsdonk et al.   NEW ENGLAND JOURNAL OF MEDICINE

Gαq Binds Two Effectors Separately in Cells: Evidence for Predetermined Signaling Pathways

(2008) Urszula Golebiewska et al.   BIOPHYSICAL JOURNAL

The Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase Inhibitor AZD6244 (ARRY-142886) Induces Growth Arrest in Melanoma Cells and Tumor Regression When Combined with Docetaxel

(2008) N. K. Haass et al.   CLINICAL CANCER RESEARCH

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

Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi

(2008) Catherine D. Van Raamsdonk et al.   NATURE