MEK inhibitors as a chemotherapeutic intervention in multiple myeloma

Phase I/II trial of the MEK1/2 inhibitor GSK1120212 (GSK212) in patients (pts) with relapsed/refractory myeloid malignancies: Evidence of activity in pts with RAS mutation.

(2017) G. Borthakur et al.   JOURNAL OF CLINICAL ONCOLOGY

Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging

(2016) Linda S. Steelman et al.   Aging-US

IκB kinase regulation of the TPL-2/ERK MAPK pathway

(2012) Thorsten Gantke et al.   IMMUNOLOGICAL REVIEWS

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

STAT3 Mediates Resistance to MEK Inhibitor through MicroRNA miR-17

(2011) B. Dai 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

Activity of XL184 (Cabozantinib), an Oral Tyrosine Kinase Inhibitor, in Patients With Medullary Thyroid Cancer

(2011) Razelle Kurzrock 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

Targeting HSP 90 Induces Apoptosis and Inhibits Critical Survival and Proliferation Pathways in Multiple Myeloma

(2011) T. Khong et al.   MOLECULAR CANCER THERAPEUTICS

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

A mechanistic rationale for MEK inhibitor therapy in myeloma based on blockade of MAF oncogene expression

(2010) C. M. Annunziata et al.   BLOOD

Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma

(2010) P. G. Richardson et al.   BLOOD

Blockade of the MEK/ERK signalling cascade by AS703026, a novel selective MEK1/2 inhibitor, induces pleiotropic anti-myeloma activity in vitro and in vivo

(2010) Kihyun Kim et al.   BRITISH JOURNAL OF HAEMATOLOGY

Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma

(2010) Ruben Niesvizky et al.   CANCER

Transcriptional Pathway Signatures Predict MEK Addiction and Response to Selumetinib (AZD6244)

(2010) J. R. Dry et al.   CANCER RESEARCH

Mechanistic principles of RAF kinase signaling

(2010) Christian M. Udell et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

Targeting the Mitogen-Activated Protein Kinase Pathway: Physiological Feedback and Drug Response

(2010) C. A. Pratilas et al.   CLINICAL 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

Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugs

(2010) Fortunato Morabito et al.   EUROPEAN JOURNAL OF HAEMATOLOGY

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

Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study

(2010) Michele Cavo et al.   LANCET

The histone deacetylase inhibitor LBH589 enhances the anti-myeloma effects of chemotherapy in vitro and in vivo

(2010) Eric Sanchez et al.   LEUKEMIA RESEARCH

KRASmutant lung cancer cells are differentially responsive to MEK inhibitor due to AKT or STAT3 activation: Implication for combinatorial approach

(2010) Young-Kwang Yoon et al.   MOLECULAR CARCINOGENESIS

BRAF Gene Amplification Can Promote Acquired Resistance to MEK Inhibitors in Cancer Cells Harboring the BRAF V600E Mutation

(2010) R. B. Corcoran et al.   Science Signaling

Inhibition of MEK signaling enhances the ability of cytarabine to induce growth arrest and apoptosis of acute myelogenous leukemia cells

(2009) Chie Nishioka et al.   APOPTOSIS

Blockade of the ERK or PI3K–Akt signaling pathway enhances the cytotoxicity of histone deacetylase inhibitors in tumor cells resistant to gefitinib or imatinib

(2009) Kei-ichi Ozaki et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

RDEA119/BAY 869766: A Potent, Selective, Allosteric Inhibitor of MEK1/2 for the Treatment of Cancer

(2009) C. Iverson et al.   CANCER RESEARCH

In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma

(2009) E. M. Ocio et al.   HAEMATOLOGICA

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

PD0325901, a Mitogen-Activated Protein Kinase Kinase Inhibitor, Produces Ocular Toxicity in a Rabbit Animal Model of Retinal Vein Occlusion

(2009) Wenhu Huang et al.   JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS

The use of novel agents in the treatment of relapsed and refractory multiple myeloma

(2009) J P Laubach et al.   LEUKEMIA

Combination of EGFR and MEK1/2 inhibitor shows synergistic effects by suppressing EGFR/HER3-dependent AKT activation in human gastric cancer cells

(2009) Y.-K. Yoon et al.   MOLECULAR CANCER THERAPEUTICS

A Mek1–Mek2 heterodimer determines the strength and duration of the Erk signal

(2009) Federica Catalanotti et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Dual-specificity MAP kinase phosphatases (MKPs) and cancer

(2008) Stephen M. Keyse   CANCER AND METASTASIS REVIEWS

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

Clinical and biological significance of RAS mutations in multiple myeloma

(2008) W J Chng et al.   LEUKEMIA

Involvement of p53 and Raf/MEK/ERK pathways in hematopoietic drug resistance

(2008) J A McCubrey et al.   LEUKEMIA

Bone marrow microenvironment and the identification of new targets for myeloma therapy

(2008) K Podar et al.   LEUKEMIA

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