NRAS mutant melanoma: biological behavior and future strategies for therapeutic management

METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM).

(2017) Caroline Robert et al.   JOURNAL OF CLINICAL ONCOLOGY

Assessment of association between BRAF-V600E mutation status in melanomas and clinical response to ipilimumab

(2012) Vafa Shahabi et al.   CANCER IMMUNOLOGY IMMUNOTHERAPY

Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer

(2012) James S. Duncan et al.   CELL

The HSP90 Inhibitor XL888 Overcomes BRAF Inhibitor Resistance Mediated through Diverse Mechanisms

(2012) K. H. T. Paraiso et al.   CLINICAL CANCER RESEARCH

RAF265 Inhibits the Growth of Advanced Human Melanoma Tumors

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

Raf Inhibitors Target Ras Spatiotemporal Dynamics

(2012) Kwang-jin Cho et al.   CURRENT BIOLOGY

Atypical Melanocytic Proliferations and New Primary Melanomas in Patients With Advanced Melanoma Undergoing SelectiveBRAFInhibition

(2012) Lisa Zimmer et al.   JOURNAL OF CLINICAL ONCOLOGY

Acquired Resistance to BRAF Inhibition Can Confer Cross-Resistance to Combined BRAF/MEK Inhibition

(2012) Kavitha Gowrishankar et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Activated Mutant NRasQ61K Drives Aberrant Melanocyte Signaling, Survival, and Invasiveness via a Rac1-Dependent Mechanism

(2012) Ang Li et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Combinations of BRAF, MEK, and PI3K/mTOR Inhibitors Overcome Acquired Resistance to the BRAF Inhibitor GSK2118436 Dabrafenib, Mediated by NRAS or MEK Mutations

(2012) J. G. Greger et al.   MOLECULAR CANCER THERAPEUTICS

The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity

(2012) Jordi Barretina et al.   NATURE

Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma

(2012) Olga Shakhova et al.   NATURE CELL BIOLOGY

Improved Survival with MEK Inhibition in BRAF-Mutated Melanoma

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

RASMutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors

(2012) Fei Su et al.   NEW ENGLAND JOURNAL OF MEDICINE

Negative Feedback and Adaptive Resistance to the Targeted Therapy of Cancer

(2012) Sarat Chandarlapaty   Cancer Discovery

Acquired and intrinsic BRAF inhibitor resistance in BRAF V600E mutant melanoma

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

NRAS mutation status is an independent prognostic factor in metastatic melanoma

(2011) John A. Jakob et al.   CANCER

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

(2011) F. Su 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

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

Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers

(2011) Hiromichi Ebi et al.   JOURNAL OF CLINICAL INVESTIGATION

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

Correlation of NRAS Mutations With Clinical Response to High-dose IL-2 in Patients With Advanced Melanoma

(2011) Richard W. Joseph et al.   JOURNAL OF IMMUNOTHERAPY

Human Cutaneous Melanomas Lacking MITF and Melanocyte Differentiation Antigens Express a Functional Axl Receptor Kinase

(2011) Marialuisa Sensi et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

Comprehensive analysis of receptor tyrosine kinase activation in human melanomas reveals autocrine signaling through IGF-1R

(2011) Kerrington R. Molhoek et al.   MELANOMA RESEARCH

Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma

(2011) K. Tworkoski et al.   MOLECULAR CANCER RESEARCH

ERK and PDE4 cooperate to induce RAF isoform switching in melanoma

(2011) Amélie Marquette et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

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

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

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

Clinical outcome and pathological features associated with NRAS mutation in cutaneous melanoma

(2011) Bianca Devitt et al.   Pigment Cell & Melanoma Research

Reversing Melanoma Cross-Resistance to BRAF and MEK Inhibitors by Co-Targeting the AKT/mTOR Pathway

(2011) Mohammad Atefi et al.   PLoS One

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

(2010) Stefan Duensing et al.   BIOCHEMICAL PHARMACOLOGY

4E-BP1 Is a Key Effector of the Oncogenic Activation of the AKT and ERK Signaling Pathways that Integrates Their Function in Tumors

(2010) Qing-Bai She et al.   CANCER CELL

A Mouse Model of Melanoma Driven by Oncogenic KRAS

(2010) C. Milagre et al.   CANCER RESEARCH

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

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

(2010) Sonja J. Heidorn et al.   CELL

Clinical Correlates of NRAS and BRAF Mutations in Primary Human Melanoma

(2010) J. A. Ellerhorst et al.   CLINICAL CANCER RESEARCH

High Frequency of p16INK4A Promoter Methylation in NRAS-Mutated Cutaneous Melanoma

(2010) Anders Jonsson et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

The Farnesyl Transferase Inhibitor Lonafarnib Inhibits mTOR Signaling and Enforces Sorafenib-Induced Apoptosis in Melanoma Cells

(2010) Heike Niessner et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

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

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

(2010) Ramin Nazarian et al.   NATURE

Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles

(2010) Mark E. Davis et al.   NATURE

Inhibition of Mutated, Activated BRAF in Metastatic Melanoma

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

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

(2010) F. Stephen Hodi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Dissection of RAS downstream pathways in melanomagenesis: a role for Ral in transformation

(2010) P J Mishra et al.   ONCOGENE

Ral activation promotes melanomagenesis

(2010) P A Zipfel et al.   ONCOGENE

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

Meenhard Herlyn

(2010) Ruth Halaban   Pigment Cell & Melanoma Research

Integrated Molecular and Clinical Analysis of AKT Activation in Metastatic Melanoma

(2009) M. A. Davies et al.   CLINICAL CANCER RESEARCH

Coexisting NRAS and BRAF Mutations in Primary Familial Melanomas with Specific CDKN2A Germline Alterations

(2009) Braslav Jovanovic et al.   JOURNAL OF INVESTIGATIVE DERMATOLOGY

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

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

BrafV600E cooperates with Pten loss to induce metastatic melanoma

(2009) David Dankort et al.   NATURE GENETICS

The PTEN-AKT3 signaling cascade as a therapeutic target in melanoma

(2009) SubbaRao V. Madhunapantula et al.   Pigment Cell & Melanoma Research

Combined Targeting of BRAF and CRAF or BRAF and PI3K Effector Pathways Is Required for Efficacy in NRAS Mutant Tumors

(2009) Bijay S. Jaiswal et al.   PLoS One

A novel AKT3 mutation in melanoma tumours and cell lines

(2008) M A Davies et al.   BRITISH JOURNAL OF CANCER

Modeling Genomic Diversity and Tumor Dependency in Malignant Melanoma

(2008) W. M. Lin et al.   CANCER RESEARCH

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

(2008) M. Cheung 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

OncogenicNRAShas multiple effects on the malignant phenotype of human melanoma cells culturedin vitro

(2008) Malihe Eskandarpour et al.   INTERNATIONAL JOURNAL OF CANCER

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

Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers

(2008) Jeffrey A Engelman et al.   NATURE MEDICINE

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

(2008) K S M Smalley et al.   ONCOGENE

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

(2008) K Boisvert-Adamo et al.   ONCOGENE

Improving Melanoma Classification by Integrating Genetic and Morphologic Features

(2008) Amaya Viros et al.   PLOS MEDICINE