Proteasome inhibition in multiple myeloma: lessons for other cancers

The coordinated action of VCP/p97 and GCN2 regulates cancer cell metabolism and proteostasis during nutrient limitation

(2019) Katarzyna Parzych et al.   ONCOGENE

The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum

(2019) G. Elif Karagöz et al.   Cold Spring Harbor Perspectives in Biology

Cholesterol and Its Metabolites in Tumor Growth: Therapeutic Potential of Statins in Cancer Treatment

(2019) Adele Chimento et al.   Frontiers in Endocrinology

Ufbp1 promotes plasma cell development and ER expansion by modulating distinct branches of UPR

(2019) Huabin Zhu et al.   Nature Communications

An HK2 antisense oligonucleotide induces synthetic lethality in HK1-HK2+ multiple myeloma

(2019) Shili Xu et al.   CANCER RESEARCH

Randomized phase 3 study of carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible, NDMM patients

(2019) Thierry Facon et al.   BLOOD

International myeloma working group consensus recommendations on imaging in monoclonal plasma cell disorders

(2019) Jens Hillengass et al.   LANCET ONCOLOGY

Selective Inhibitors of Nuclear Export in the Treatment of Hematologic Malignancies

(2019) Alessandro Allegra et al.   Clinical Lymphoma Myeloma & Leukemia

Exportin 1 inhibition induces nerve growth factor receptor expression to inhibit the NF-kB pathway in preclinical models of pediatric high-grade glioma

(2019) John A. DeSisto et al.   MOLECULAR CANCER THERAPEUTICS

Mechanistic insights into ER-associated protein degradation

(2018) Xudong Wu et al.   CURRENT OPINION IN CELL BIOLOGY

Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

(2018) David S. Siegel et al.   JOURNAL OF CLINICAL ONCOLOGY

Spectrum and functional validation of PSMB5 mutations in multiple myeloma

(2018) Santiago Barrio et al.   LEUKEMIA

An engineered, quantifiable in vitro model for analysing the effect of proteostasis-targeting drugs on tissue physical properties

(2018) Sandra Loaiza et al.   BIOMATERIALS

Promising activity of nelfinavir-bortezomib-dexamethasone (NeVd) in proteasome inhibitor-refractory multiple myeloma

(2018) Christoph Driessen et al.   BLOOD

The immunoproteasome and thymoproteasome: functions, evolution and human disease

(2018) Shigeo Murata et al.   NATURE IMMUNOLOGY

Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response

(2018) Akito Nakamura et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma

(2018) V. Desantis et al.   Translational Oncology

Oral ixazomib maintenance following autologous stem cell transplantation (TOURMALINE-MM3): a double-blind, randomised, placebo-controlled phase 3 trial

(2018) Meletios A Dimopoulos et al.   LANCET

Development of GLUT4-selective antagonists for multiple myeloma therapy

(2017) Changyong Wei et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Carfilzomib or bortezomib in relapsed or refractory multiple myeloma (ENDEAVOR): an interim overall survival analysis of an open-label, randomised, phase 3 trial

(2017) Meletios A Dimopoulos et al.   LANCET ONCOLOGY

Carfilzomib resistance due to ABCB1/MDR1 overexpression is overcome by nelfinavir and lopinavir in multiple myeloma

(2017) A Besse et al.   LEUKEMIA

Alcohol-abuse drug disulfiram targets cancer via p97 segregase adaptor NPL4

(2017) Zdenek Skrott et al.   NATURE

Modulating the therapeutic response of tumours to dietary serine and glycine starvation

(2017) Oliver D. K. Maddocks et al.   NATURE

Deubiquitylating enzymes and drug discovery: emerging opportunities

(2017) Jeanine A. Harrigan et al.   NATURE REVIEWS DRUG DISCOVERY

The Ubiquitin Code in the Ubiquitin-Proteasome System and Autophagy

(2017) Yong Tae Kwon et al.   TRENDS IN BIOCHEMICAL SCIENCES

Glutaminase inhibitor CB-839 synergizes with carfilzomib in resistant multiple myeloma cells

(2017) Ravyn M. Thompson et al.   Oncotarget

Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress

(2017) Craig T. Wallington-Beddoe et al.   Oncotarget

Endoplasmic reticulum stress signaling and chemotherapy resistance in solid cancers

(2017) T Avril et al.   Oncogenesis

Dependence on glutamine uptake and glutamine addiction characterize myeloma cells: a new attractive target

(2016) M. Bolzoni et al.   BLOOD

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study

(2016) Meletios A Dimopoulos et al.   LANCET ONCOLOGY

PKM2 and other key regulators of Warburg effect positively correlate with CD147 (EMMPRIN) gene expression and predict survival in multiple myeloma

(2016) S Panchabhai et al.   LEUKEMIA

Nuclear Export of Ubiquitinated Proteins Determines the Sensitivity of Colorectal Cancer to Proteasome Inhibitor

(2016) Tingyu Wu et al.   MOLECULAR CANCER THERAPEUTICS

The amino acid sensor GCN2 controls gut inflammation by inhibiting inflammasome activation

(2016) Rajesh Ravindran et al.   NATURE

Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response

(2016) Julie Tellier et al.   NATURE IMMUNOLOGY

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma

(2016) Philippe Moreau et al.   NEW ENGLAND JOURNAL OF MEDICINE

In vivo aspects of protein folding and quality control

(2016) D. Balchin et al.   SCIENCE

XPO1 inhibitor combination therapy with bortezomib or carfilzomib induces nuclear localization of IκBα and overcomes acquired proteasome inhibitor resistance in human multiple myeloma

(2016) Joel G. Turner et al.   Oncotarget

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming

(2016) Irene Riz et al.   Oncotarget

Targeting p97 to Disrupt Protein Homeostasis in Cancer

(2016) Pratikkumar Harsukhbhai Vekaria et al.   Frontiers in Oncology

The Biology of Proteostasis in Aging and Disease

(2015) Johnathan Labbadia et al.   Annual Review of Biochemistry

A plastic SQSTM1/p62-dependent autophagic reserve maintains proteostasis and determines proteasome inhibitor susceptibility in multiple myeloma cells

(2015) Enrico Milan et al.   Autophagy

Metabolic Signature Identifies Novel Targets for Drug Resistance in Multiple Myeloma

(2015) P. Maiso et al.   CANCER RESEARCH

GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2

(2015) Jiangbin Ye et al.   GENES & DEVELOPMENT

Surviving protein quality control catastrophes - from cells to organisms

(2015) K. Schneider et al.   JOURNAL OF CELL SCIENCE

Halting pro-survival autophagy by TGFβ inhibition in bone marrow fibroblasts overcomes bortezomib resistance in multiple myeloma patients

(2015) M A Frassanito et al.   LEUKEMIA

Mitochondrial thioredoxin reductase regulates major cytotoxicity pathways of proteasome inhibitors in multiple myeloma cells

(2015) E E Fink et al.   LEUKEMIA

Pharmacologic screens reveal metformin that suppresses GRP78-dependent autophagy to enhance the anti-myeloma effect of bortezomib

(2015) S Jagannathan et al.   LEUKEMIA

Plasma fatty acid profile in multiple myeloma patients

(2015) Artur Jurczyszyn et al.   LEUKEMIA RESEARCH

Nutrient-sensing mechanisms and pathways

(2015) Alejo Efeyan et al.   NATURE

Proteostasis control by the unfolded protein response

(2015) Claudio Hetz et al.   NATURE CELL BIOLOGY

Proteostasis and aging

(2015) Susmita Kaushik et al.   NATURE MEDICINE

Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma

(2015) A. Keith Stewart et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting glutamine metabolism in multiple myeloma enhances BIM binding to BCL-2 eliciting synthetic lethality to venetoclax

(2015) R Bajpai et al.   ONCOGENE

Phosphorylation of eIF2  triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma

(2015) J. Wengrod et al.   Science Signaling

Dysregulated metabolism contributes to oncogenesis

(2015) Matthew D. Hirschey et al.   SEMINARS IN CANCER BIOLOGY

Type 2 diabetes as a protein misfolding disease

(2015) Abhisek Mukherjee et al.   TRENDS IN MOLECULAR MEDICINE

Inadequate fine-tuning of protein synthesis and failure of amino acid homeostasis following inhibition of the ATPase VCP/p97

(2015) K Parzych et al.   Cell Death & Disease

Phosphorylation of eIF2  triggered by mTORC1 inhibition and PP6C activation is required for autophagy and is aberrant in PP6C-mutated melanoma

(2015) J. Wengrod et al.   Science Signaling

Association between metformin use and progression of monoclonal gammopathy of undetermined significance to multiple myeloma in US veterans with diabetes mellitus: a population-based retrospective cohort study

(2015) Su-Hsin Chang et al.   Lancet Haematology

Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome Structure

(2015) David S. Pitcher et al.   EBioMedicine

Targeting hypoxia-inducible factor-1α (HIF-1α) in combination with antiangiogenic therapy: A phase I trial of bortezomib plus bevacizumab

(2015) Gerald S. Falchook et al.   Oncotarget

Amino Acid Deprivation Promotes Tumor Angiogenesis through the GCN2/ATF4 Pathway

(2015) Yugang Wang et al.   NEOPLASIA

Combined autophagy and proteasome inhibition

(2014) Dan T Vogl et al.   Autophagy

Enhanced rate of degradation of basic proteins by 26S immunoproteasomes

(2014) Mary Raule et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Keeping the eIF2 alpha kinase Gcn2 in check

(2014) Beatriz A. Castilho et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl-1 and induces apoptosis in multiple myeloma

(2014) J. Kummetha Venkata et al.   BLOOD

Proteotoxic crisis, the ubiquitin-proteasome system, and cancer therapy

(2014) Raymond J Deshaies   BMC BIOLOGY

Recent advances and future directions in targeting the secretory apparatus in multiple myeloma

(2014) Holger W. Auner et al.   BRITISH JOURNAL OF HAEMATOLOGY

Endoplasmic Reticulum Stress in Malignancy

(2014) Hanna J. Clarke et al.   CANCER CELL

Targeting the Metabolic Plasticity of Multiple Myeloma with FDA-Approved Ritonavir and Metformin

(2014) S. Dalva-Aydemir et al.   CLINICAL CANCER RESEARCH

Proteasome-Mediated Processing of Nrf1 Is Essential for Coordinate Induction of All Proteasome Subunits and p97

(2014) Zhe Sha et al.   CURRENT BIOLOGY

Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases

(2014) Claudio Hetz et al.   NATURE REVIEWS NEUROSCIENCE

p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition

(2014) Senthil K Radhakrishnan et al.   eLife

An Overview of Autophagy: Morphology, Mechanism, and Regulation

(2013) Katherine R. Parzych et al.   ANTIOXIDANTS & REDOX SIGNALING

The role of autophagy in plasma cell ontogenesis

(2013) Niccolò Pengo et al.   Autophagy

Targeting the ubiquitin proteasome system in haematological malignancies

(2013) Lisa J. Crawford et al.   BLOOD REVIEWS

PDK1 inhibition is a novel therapeutic target in multiple myeloma

(2013) S Fujiwara et al.   BRITISH JOURNAL OF CANCER

Dichloroacetate inhibits aerobic glycolysis in multiple myeloma cells and increases sensitivity to bortezomib

(2013) W Y Sanchez et al.   BRITISH JOURNAL OF CANCER

Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma

(2013) Chungyee Leung-Hagesteijn et al.   CANCER CELL

Preventing the autophagic survival response by inhibition of calpain enhances the cytotoxic activity of bortezomib in vitro and in vivo

(2013) Aluvia M. Escalante et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Multiple Myeloma Patients Have a Specific Serum Metabolomic Profile That Changes after Achieving Complete Remission

(2013) L. Puchades-Carrasco et al.   CLINICAL CANCER RESEARCH

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

(2013) Anne-Laure Huber et al.   MOLECULAR CELL

The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression

(2013) Wafa B’chir et al.   NUCLEIC ACIDS RESEARCH

Combined Inhibition of p97 and the Proteasome Causes Lethal Disruption of the Secretory Apparatus in Multiple Myeloma Cells

(2013) Holger W. Auner et al.   PLoS One

Cancer Genome Landscapes

(2013) B. Vogelstein et al.   SCIENCE

Structural Basis of the Unfolded Protein Response

(2012) Alexei Korennykh et al.   Annual Review of Cell and Developmental Biology

Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma

(2012) A. Chaidos et al.   BLOOD

Multiple myeloma exhibits novel dependence on GLUT4, GLUT8, and GLUT11: implications for glucose transporter-directed therapy

(2012) S. K. McBrayer et al.   BLOOD

Blockade of XBP1 splicing by inhibition of IRE1  is a promising therapeutic option in multiple myeloma

(2012) N. Mimura et al.   BLOOD

Iron increases the susceptibility of multiple myeloma cells to bortezomib

(2012) A. Campanella et al.   HAEMATOLOGICA

High Rate of Antibody Secretion Is not Integral to Plasma Cell Differentiation as Revealed by XBP-1 Deficiency

(2012) N. Taubenheim et al.   JOURNAL OF IMMUNOLOGY

Pivotal Advance: Protein synthesis modulates responsiveness of differentiating and malignant plasma cells to proteasome inhibitors

(2012) Simone Cenci et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Failure of Amino Acid Homeostasis Causes Cell Death following Proteasome Inhibition

(2012) Amila Suraweera et al.   MOLECULAR CELL

Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system

(2012) Hemmo Meyer et al.   NATURE CELL BIOLOGY

Inhibition of Fatty Acid Metabolism Reduces Human Myeloma Cells Proliferation

(2012) José Manuel Tirado-Vélez et al.   PLoS One

Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicing

(2012) M Ri et al.   Blood Cancer Journal

ER stress modulates cellular metabolism

(2011) Xiaoli Wang et al.   BIOCHEMICAL JOURNAL

Activation of ATF4 mediates unwanted Mcl-1 accumulation by proteasome inhibition

(2011) J. Hu et al.   BLOOD

Nonproteasomal Targets of the Proteasome Inhibitors Bortezomib and Carfilzomib: a Link to Clinical Adverse Events

(2011) S. Arastu-Kapur et al.   CLINICAL CANCER RESEARCH

Response of myeloma to the proteasome inhibitor bortezomib is correlated with the unfolded protein response regulator XBP-1

(2011) S. C. W. Ling et al.   HAEMATOLOGICA

Metabolomics of B to Plasma Cell Differentiation

(2011) Jose Manuel Garcia-Manteiga et al.   JOURNAL OF PROTEOME RESEARCH

Mice completely lacking immunoproteasomes show major changes in antigen presentation

(2011) Eleanor Z Kincaid et al.   NATURE IMMUNOLOGY

Compromising the Unfolded Protein Response Induces Autophagy-Mediated Cell Death in Multiple Myeloma Cells

(2011) Anne-Sophie Michallet et al.   PLoS One

The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation

(2011) P. Walter et al.   SCIENCE

Ubiquitylation in ERAD: Reversing to Go Forward?

(2011) Yien Che Tsai et al.   PLOS BIOLOGY

The life span of short-lived plasma cells is partly determined by a block on activation of apoptotic caspases acting in combination with endoplasmic reticulum stress

(2010) H. W. Auner et al.   BLOOD

Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma

(2010) I. Papandreou et al.   BLOOD

Proteostenosis and plasma cell pathophysiology

(2010) Simone Cenci et al.   CURRENT OPINION IN CELL BIOLOGY

The GCN2-ATF4 pathway is critical for tumour cell survival and proliferation in response to nutrient deprivation

(2010) Jiangbin Ye et al.   EMBO JOURNAL

Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial

(2010) Maria-Victoria Mateos et al.   JOURNAL OF CLINICAL ONCOLOGY

Transcription Factor Nrf1 Mediates the Proteasome Recovery Pathway after Proteasome Inhibition in Mammalian Cells

(2010) Senthil K. Radhakrishnan et al.   MOLECULAR CELL

Proteasomal Degradation Is Transcriptionally Controlled by TCF11 via an ERAD-Dependent Feedback Loop

(2010) Janos Steffen et al.   MOLECULAR CELL

The proteasome load versus capacity balance determines apoptotic sensitivity of multiple myeloma cells to proteasome inhibition

(2009) G. Bianchi et al.   BLOOD

GCN2 Protein Kinase Is Required to Activate Amino Acid Deprivation Responses in Mice Treated with the Anti-cancer Agent l-Asparaginase

(2009) Piyawan Bunpo et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Biogenesis of secretory organelles during B cell differentiation

(2009) Semra J. Kirk et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Effect of autophagy on multiple myeloma cell viability

(2009) B. Hoang et al.   MOLECULAR CANCER THERAPEUTICS

Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat

(2009) V. I. Perez et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ERAD inhibitors integrate ER stress with an epigenetic mechanism to activate BH3-only protein NOXA in cancer cells

(2009) Q. Wang et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1

(2008) D. H. Shin et al.   BLOOD

Molecular basis of bortezomib resistance: proteasome subunit  5 (PSMB5) gene mutation and overexpression of PSMB5 protein

(2008) R. Oerlemans et al.   BLOOD

One step at a time: endoplasmic reticulum-associated degradation

(2008) Shruthi S. Vembar et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Bortezomib plus Melphalan and Prednisone for Initial Treatment of Multiple Myeloma

(2008) Jesús F. San Miguel et al.   NEW ENGLAND JOURNAL OF MEDICINE