Targeting Mutant BRAF in Melanoma

Phase I/II study of GSK2118436, a selective inhibitor of oncogenic mutant BRAF kinase, in patients with metastatic melanoma and other solid tumors.

(2017) R. Kefford et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase I/II study to assess safety, pharmacokinetics, and efficacy of the oral MEK 1/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral BRAF inhibitor GSK2118436 (GSK436).

(2017) J. R. Infante et al.   JOURNAL OF CLINICAL ONCOLOGY

Pharmacodynamic Characterization of the Efficacy Signals Due to Selective BRAF Inhibition with PLX4032 in Malignant Melanoma

(2015) William D. Tap et al.   NEOPLASIA

Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma

(2011) Inna V. Fedorenko et al.   BIOCHEMICAL PHARMACOLOGY

Oncogenic BRAF Induces Melanoma Cell Invasion by Downregulating the cGMP-Specific Phosphodiesterase PDE5A

(2011) Imanol Arozarena et al.   CANCER CELL

Combinatorial Treatments That Overcome PDGFR -Driven Resistance of Melanoma Cells to V600EB-RAF Inhibition

(2011) H. Shi et al.   CANCER RESEARCH

PTEN Loss Confers BRAF Inhibitor Resistance to Melanoma Cells through the Suppression of BIM Expression

(2011) K. H. T. Paraiso et al.   CANCER RESEARCH

Protein Kinase D3 Sensitizes RAF Inhibitor RAF265 in Melanoma Cells by Preventing Reactivation of MAPK Signaling

(2011) J. Chen et al.   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

Prognostic and Clinicopathologic Associations of OncogenicBRAFin Metastatic Melanoma

(2011) Georgina V. Long et al.   JOURNAL OF CLINICAL ONCOLOGY

RASMutations Are Associated With the Development of Cutaneous Squamous Cell Tumors in Patients Treated With RAF Inhibitors

(2011) Patrick A. Oberholzer et al.   JOURNAL OF CLINICAL ONCOLOGY

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

(2011) Poulikos I. Poulikakos et al.   NATURE

Ipilimumab

(2011) Vernon K. Sondak et al.   NATURE REVIEWS DRUG DISCOVERY

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

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

Concurrent loss of the PTEN and RB1 tumor suppressors attenuates RAF dependence in melanomas harboring V600EBRAF

(2011) F Xing et al.   ONCOGENE

Meeting report from the 2011 international melanoma congress, Tampa, Florida

(2011) Keiran S. M. Smalley et al.   Pigment Cell & Melanoma Research

Embryonic stem-cell-preconditioned microenvironment induces loss of cancer cell properties in human melanoma cells

(2011) Myoung Ok Kim et al.   Pigment Cell & Melanoma Research

Building on a foundation of VEGF and mTOR targeted agents in renal cell carcinoma

(2010) Keith T. Flaherty et al.   BIOCHEMICAL PHARMACOLOGY

Targeted therapies of gastrointestinal stromal tumors (GIST)—The next frontiers

(2010) Stefan Duensing et al.   BIOCHEMICAL PHARMACOLOGY

Recovery of phospho-ERK activity allows melanoma cells to escape from BRAF inhibitor therapy

(2010) K H T Paraiso et al.   BRITISH JOURNAL OF CANCER

Acquired Resistance to BRAF Inhibitors Mediated by a RAF Kinase Switch in Melanoma Can Be Overcome by Cotargeting MEK and IGF-1R/PI3K

(2010) Jessie Villanueva et al.   CANCER CELL

Basal and Treatment-Induced Activation of AKT Mediates Resistance to Cell Death by AZD6244 (ARRY-142886) in Braf-Mutant Human Cutaneous Melanoma Cells

(2010) Y. N. V. Gopal et al.   CANCER RESEARCH

Akt3-Mediated Resistance to Apoptosis in B-RAF-Targeted Melanoma Cells

(2010) Y. Shao et al.   CANCER RESEARCH

Selective BRAFV600E Inhibition Enhances T-Cell Recognition of Melanoma without Affecting Lymphocyte Function

(2010) A. Boni et al.   CANCER RESEARCH

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

(2010) Sonja J. Heidorn et al.   CELL

MEK-Independent Survival of B-RAFV600E Melanoma Cells Selected for Resistance to Apoptosis Induced by the RAF Inhibitor PLX4720

(2010) C. C. Jiang 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

Incidence of the V600K mutation among melanoma patients with BRAF mutations, and potential therapeutic response to the specific BRAF inhibitor PLX4032

(2010) Jill C Rubinstein et al.   Journal of Translational Medicine

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

(2010) Poulikos I. Poulikakos et al.   NATURE

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma

(2010) Gideon Bollag 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

Hyperactivation of MEK–ERK1/2 signaling and resistance to apoptosis induced by the oncogenic B-RAF inhibitor, PLX4720, in mutant N-RAS melanoma cells

(2010) F M Kaplan et al.   ONCOGENE

Taking stock of translational research in melanoma at the 2010 Society for Melanoma Research Congress

(2010) Keith T. Flaherty   Pigment Cell & Melanoma Research

Meeting report from the 7th International Melanoma Congress, Sydney, November, 2010

(2010) P. Hersey et al.   Pigment Cell & Melanoma Research

PLX4032, a potent inhibitor of the B-Raf V600E oncogene, selectively inhibits V600E-positive melanomas

(2010) John T. Lee et al.   Pigment Cell & Melanoma Research

PLX4032, a selective BRAFV600E kinase inhibitor, activates the ERK pathway and enhances cell migration and proliferation of BRAFWT melanoma cells

(2010) Ruth Halaban et al.   Pigment Cell & Melanoma Research

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

Gatekeeper Mutations Mediate Resistance to BRAF-Targeted Therapies

(2010) S. Whittaker et al.   Science Translational Medicine

Apoptosis of human melanoma cells induced by inhibition of B-RAFV600E involves preferential splicing of bimS

(2010) C C Jiang et al.   Cell Death & Disease

Mitogen-Activated Protein Kinase Inhibition Induces Translocation of Bmf to Promote Apoptosis in Melanoma

(2009) M. W. VanBrocklin et al.   CANCER RESEARCH

Rnd3 Regulation of the Actin Cytoskeleton Promotes Melanoma Migration and Invasive Outgrowth in Three Dimensions

(2009) R. M. Klein et al.   CANCER RESEARCH

Expression of Sorafenib Targets in Melanoma Patients Treated with Carboplatin, Paclitaxel and Sorafenib

(2009) L. Jilaveanu et al.   CLINICAL CANCER RESEARCH

BRAF Signaling and Targeted Therapies in Melanoma

(2009) Nathalie Dhomen et al.   HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA

Randomized Phase II Trial Evaluating Two Paclitaxel and Cisplatin–Containing Chemoradiation Regimens As Adjuvant Therapy in Resected Gastric Cancer (RTOG-0114)

(2009) Gary K. Schwartz et al.   JOURNAL OF CLINICAL ONCOLOGY

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

Mcl-1 Is Required for Melanoma Cell Resistance to Anoikis

(2009) K. Boisvert-Adamo et al.   MOLECULAR CANCER RESEARCH

BrafV600E cooperates with Pten loss to induce metastatic melanoma

(2009) David Dankort et al.   NATURE GENETICS

Smoothened Mutation Confers Resistance to a Hedgehog Pathway Inhibitor in Medulloblastoma

(2009) R. L. Yauch et al.   SCIENCE

Akt3 and Mutant V600EB-Raf Cooperate to Promote Early Melanoma Development

(2008) M. Cheung et al.   CANCER RESEARCH

Elevated CRAF as a Potential Mechanism of Acquired Resistance to BRAF Inhibition in Melanoma

(2008) C. Montagut et al.   CANCER RESEARCH

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

Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas

(2008) K. S.M. Smalley et al.   MOLECULAR CANCER THERAPEUTICS

CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations

(2008) K S M Smalley et al.   ONCOGENE

The role of PTEN signaling perturbations in cancer and in targeted therapy

(2008) M Keniry et al.   ONCOGENE

Mutant B-RAF mediates resistance to anoikis via Bad and Bim

(2008) K Boisvert-Adamo et al.   ONCOGENE

Oncogenic BRAFV600E inhibits BIM expression to promote melanoma cell survival

(2008) Robert A. Cartlidge et al.   Pigment Cell & Melanoma Research

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

Improving Melanoma Classification by Integrating Genetic and Morphologic Features

(2008) Amaya Viros et al.   PLOS MEDICINE

B-RAF Regulation of Rnd3 Participates in Actin Cytoskeletal and Focal Adhesion Organization

(2007) R. Matthew Klein et al.   MOLECULAR BIOLOGY OF THE CELL