That which does not kill me makes me stronger; combining ERK1/2 pathway inhibitors and BH3 mimetics to kill tumour cells and prevent acquired resistance

Bcl-2/Bcl-xL Inhibition Increases the Efficacy of MEK Inhibition Alone and in Combination with PI3 Kinase Inhibition in Lung and Pancreatic Tumor Models

(2013) N. Tan et al.   MOLECULAR CANCER THERAPEUTICS

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

(2013) Meghna Das Thakur et al.   NATURE

Selective RAF inhibitor impairs ERK1/2 phosphorylation and growth in mutant NRAS, vemurafenib-resistant melanoma cells

(2013) Kaitlyn Le et al.   Pigment Cell & Melanoma Research

The BH3 mimetic ABT-263 synergizes with the MEK1/2 inhibitor selumetinib/AZD6244 to promote BIM-dependent tumour cell death and inhibit acquired resistance

(2012) Matthew J. Sale et al.   BIOCHEMICAL JOURNAL

Cutaneous manifestations of dabrafenib (GSK2118436): a selective inhibitor of mutant BRAF in patients with metastatic melanoma

(2012) R.M. Anforth et al.   BRITISH JOURNAL OF DERMATOLOGY

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

Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS Mutant Cancer Models

(2012) Ryan B. Corcoran et al.   CANCER CELL

Dual Inhibition of Bcl-2 and Bcl-xL Strikingly Enhances PI3K Inhibition-Induced Apoptosis in Human Myeloid Leukemia Cells through a GSK3- and Bim-Dependent Mechanism

(2012) M. Rahmani et al.   CANCER RESEARCH

The BH3-mimetic ABT-737 sensitizes human melanoma cells to apoptosis induced by selective BRAF inhibitors but does not reverse acquired resistance

(2012) D. Wroblewski et al.   CARCINOGENESIS

Converting Cancer Therapies into Cures: Lessons from Infectious Diseases

(2012) Michael S. Glickman et al.   CELL

Src tyrosine kinase inhibits apoptosis through the Erk1/2- dependent degradation of the death accelerator Bik

(2012) J Lopez et al.   CELL DEATH AND DIFFERENTIATION

Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer

(2012) C. M. Rudin et al.   CLINICAL CANCER RESEARCH

Phase II Efficacy and Pharmacogenomic Study of Selumetinib (AZD6244; ARRY-142886) in Iodine-131 Refractory Papillary Thyroid Carcinoma with or without Follicular Elements

(2012) D. N. Hayes et al.   CLINICAL CANCER RESEARCH

Reactivation of Mitogen-activated Protein Kinase (MAPK) Pathway by FGF Receptor 3 (FGFR3)/Ras Mediates Resistance to Vemurafenib in Human B-RAF V600E Mutant Melanoma

(2012) Vipin Yadav et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study

(2012) Pasi A Jänne et al.   LANCET ONCOLOGY

Phosphoinositide 3-kinase/AKT/mTORC1/2 Signaling Determines Sensitivity of Burkitt's Lymphoma Cells to BH3 mimetics

(2012) L. C. Spender et al.   MOLECULAR CANCER RESEARCH

Abstract A229: BRAF inhibitors upregulate EGFR ligands: A molecular link to RAF inhibitor-induced cutaneous squamous cell carcinomas.

(2012) Y. Ma et al.   MOLECULAR CANCER THERAPEUTICS

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

ERK Inhibition Overcomes Acquired Resistance to MEK Inhibitors

(2012) G. Hatzivassiliou et al.   MOLECULAR CANCER THERAPEUTICS

Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

(2012) Anirudh Prahallad et al.   NATURE

Vemurafenib: the first drug approved for BRAF-mutant cancer

(2012) Gideon Bollag et al.   NATURE REVIEWS DRUG DISCOVERY

Progression of RAS-Mutant Leukemia during RAF Inhibitor Treatment

(2012) Margaret K. Callahan et al.   NEW ENGLAND JOURNAL OF MEDICINE

Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib

(2012) Jeffrey A. Sosman 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

Mechanisms of acquired resistance to ERK1/2 pathway inhibitors

(2012) A S Little et al.   ONCOGENE

EMT as the ultimate survival mechanism of cancer cells

(2012) Neha Tiwari et al.   SEMINARS IN CANCER BIOLOGY

ERK2 phosphorylation of serine 77 regulates Bmf pro-apoptotic activity

(2012) Y Shao et al.   Cell Death & Disease

Melanoma whole-exome sequencing identifies V600E B-RAF amplification-mediated acquired B-RAF inhibitor resistance

(2012) Hubing Shi et al.   Nature Communications

EGFR-Mediated Reactivation of MAPK Signaling Contributes to Insensitivity of BRAF -Mutant Colorectal Cancers to RAF Inhibition with Vemurafenib

(2012) Ryan B. Corcoran et al.   Cancer Discovery

Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma

(2012) Maria R. Girotti et al.   Cancer Discovery

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

(2011) F. Su et al.   CANCER RESEARCH

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

Skin Tumors Induced by Sorafenib; Paradoxic RAS-RAF Pathway Activation and Oncogenic Mutations of HRAS, TP53, and TGFBR1

(2011) J. P. Arnault 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

A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy

(2011) György Bodoky et al.   INVESTIGATIONAL NEW DRUGS

Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling

(2011) Nikhil Wagle et al.   JOURNAL OF CLINICAL ONCOLOGY

Substantial Susceptibility of Chronic Lymphocytic Leukemia to BCL2 Inhibition: Results of a Phase I Study of Navitoclax in Patients With Relapsed or Refractory Disease

(2011) Andrew W. Roberts et al.   JOURNAL OF CLINICAL ONCOLOGY

MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex

(2011) M Konopleva et al.   LEUKEMIA

A phase II study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in relapsed small cell lung cancer

(2011) Paul K. Paik et al.   LUNG CANCER

Oncogenic Ras-Induced Expression of Noxa and Beclin-1 Promotes Autophagic Cell Death and Limits Clonogenic Survival

(2011) Mohamed Elgendy et al.   MOLECULAR CELL

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

(2011) Poulikos I. Poulikakos et al.   NATURE

BRAFMutations in Hairy-Cell Leukemia

(2011) Enrico Tiacci et al.   NEW ENGLAND JOURNAL OF MEDICINE

Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

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

Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer

(2011) E P Booy et al.   ONCOGENE

Predominant requirement of Bax for apoptosis in HCT116 cells is determined by Mcl-1's inhibitory effect on Bak

(2011) C Wang et al.   ONCOGENE

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

BIM Expression in Treatment-Naive Cancers Predicts Responsiveness to Kinase Inhibitors

(2011) A. C. Faber et al.   Cancer Discovery

The BRAF V600E mutation is an independent prognostic factor for survival in stage II and stage III colon cancer patients

(2010) A. Fariña-Sarasqueta et al.   ANNALS OF ONCOLOGY

Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1

(2010) D. Yecies et al.   BLOOD

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

A phase I study of obatoclax mesylate, a Bcl-2 antagonist, plus topotecan in solid tumor malignancies

(2010) Paul K. Paik et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

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

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

Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity

(2010) Wyndham H Wilson et al.   LANCET ONCOLOGY

The BCL-2 Family Reunion

(2010) Jerry E. Chipuk et al.   MOLECULAR CELL

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

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

Mitochondria and cell death: outer membrane permeabilization and beyond

(2010) Stephen W. G. Tait et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

An ERK-dependent pathway to Noxa expression regulates apoptosis by platinum-based chemotherapeutic drugs

(2010) C Sheridan et al.   ONCOGENE

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

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

Gatekeeper Mutations Mediate Resistance to BRAF-Targeted Therapies

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

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

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

Epithelial to Mesenchymal Transition Contributes to Drug Resistance in Pancreatic Cancer

(2009) T. Arumugam et al.   CANCER RESEARCH

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

5-Year Survival in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia in a Randomized, Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen

(2009) Susan O'Brien et al.   JOURNAL OF CLINICAL ONCOLOGY

KRASandBRAFMutations in Advanced Colorectal Cancer Are Associated With Poor Prognosis but Do Not Preclude Benefit From Oxaliplatin or Irinotecan: Results From the MRC FOCUS Trial

(2009) Susan D. Richman et al.   JOURNAL OF CLINICAL ONCOLOGY

Phase III randomised study of dexamethasone with or without oblimersen sodium for patients with advanced multiple myeloma

(2009) Asher A. Chanan-Khan et al.   LEUKEMIA & LYMPHOMA

Synergy between phosphatidylinositol 3-kinase/Akt pathway and Bcl-xL in the control of apoptosis in adenocarcinoma cells of the lung

(2009) J. Qian et al.   MOLECULAR CANCER THERAPEUTICS

BRAFMutation in Metastatic Colorectal Cancer

(2009) Jolien Tol et al.   NEW ENGLAND JOURNAL OF MEDICINE

Mimicking the BH3 domain to kill cancer cells

(2009) T Ni Chonghaile et al.   ONCOGENE

MEK1 mutations confer resistance to MEK and B-RAF inhibition

(2009) C. M. Emery et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phase I study of obatoclax mesylate (GX15-070), a small molecule pan-Bcl-2 family antagonist, in patients with advanced chronic lymphocytic leukemia

(2008) S. M. O'Brien et al.   BLOOD

Mechanisms of Antileukemic Activity of the Novel Bcl-2 Homology Domain-3 Mimetic GX15-070 (Obatoclax)

(2008) M. Konopleva et al.   CANCER RESEARCH

ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor

(2008) C. Tse 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

Tumour cell survival signalling by the ERK1/2 pathway

(2008) K Balmanno et al.   CELL DEATH AND DIFFERENTIATION

Oncogenic B-RafV600EInhibits Apoptosis and Promotes ERK-dependent Inactivation of Bad and Bim

(2008) Clare Sheridan et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Treatment of B-RAF mutant human tumor cells with a MEK inhibitor requires Bim and is enhanced by a BH3 mimetic

(2008) Mark S. Cragg et al.   JOURNAL OF CLINICAL INVESTIGATION

Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway

(2008) W Zhang et al.   LEUKEMIA

Repression of PTEN Phosphatase by Snail1 Transcriptional Factor during Gamma Radiation-Induced Apoptosis

(2008) M. Escriva et al.   MOLECULAR AND CELLULAR BIOLOGY

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

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

ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation

(2008) Jer-Yen Yang et al.   NATURE CELL BIOLOGY

Colorectal cancer cells with the BRAFV600E mutation are addicted to the ERK1/2 pathway for growth factor-independent survival and repression of BIM

(2008) J A Wickenden et al.   ONCOGENE

EGFR Tyrosine Kinase Inhibitors in Lung Cancer: An Evolving Story

(2007) Lecia V. Sequist et al.   Annual Review of Medicine