Harnessing TRAIL-induced cell death for cancer therapy: a long walk with thrilling discoveries

What can we learn from mice lacking pro-survival BCL-2 proteins to advance BH3 mimetic drugs for cancer therapy?

(2022) Kerstin Brinkmann et al.   CELL DEATH AND DIFFERENTIATION

A preclinical platform for assessing antitumor effects and systemic toxicities of cancer drug targets

(2022) Xiang Li et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Hexavalent TRAIL fusion protein eftozanermin alfa optimally clusters apoptosis-inducing TRAIL receptors to induce on-target antitumor activity in solid tumors

(2021) Darren C Phillips et al.   CANCER RESEARCH

Cryo-EM structural analysis of FADD:Caspase-8 complexes defines the catalytic dimer architecture for co-ordinated control of cell fate

(2021) Joanna L. Fox et al.   Nature Communications

Proteasome inhibition triggers the formation of TRAIL receptor 2 platforms for caspase-8 activation that accumulate in the cytosol

(2021) Christian T. Hellwig et al.   CELL DEATH AND DIFFERENTIATION

Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

(2021) Antonella Montinaro et al.   CELL DEATH AND DIFFERENTIATION

The MYC oncogene — the grand orchestrator of cancer growth and immune evasion

(2021) Renumathy Dhanasekaran et al.   Nature Reviews Clinical Oncology

PI3K inhibitors are finally coming of age

(2021) Bart Vanhaesebroeck et al.   NATURE REVIEWS DRUG DISCOVERY

Future Therapeutic Directions for Smac-Mimetics

(2020) Emma Morrish et al.   Cells

TRAIL and Cancer Immunotherapy: Take a Walk on the Short Side

(2020) Diego de Miguel et al.   CLINICAL CANCER RESEARCH

Dual Epitope Targeting and Enhanced Hexamerization by DR5 Antibodies as a Novel Approach to Induce Potent Antitumor Activity Through DR5 Agonism

(2020) Marije B. Overdijk et al.   MOLECULAR CANCER THERAPEUTICS

Exosomes derived from Vδ2-T cells control Epstein-Barr virus–associated tumors and induce T cell antitumor immunity

(2020) Xiwei Wang et al.   Science Translational Medicine

Targeting Alterations in the RAF–MEK Pathway

(2019) Rona Yaeger et al.   Cancer Discovery

First-in-Human Study of Abbv-621, a TRAIL Receptor Agonist Fusion Protein, in Patients (Pts) with Relapsed/Refractory (RR) Acute Myeloid Leukemia (AML) and Diffuse Large B-Cell Lymphoma (DLBCL)

(2019) Maja J.A. de Jonge et al.   BLOOD

Regulation of TNF-Related Apoptosis-Inducing Ligand Signaling by Glycosylation

(2018) Olivier Micheau   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Paving TRAIL’s Path with Ubiquitin

(2018) Elodie Lafont et al.   TRENDS IN BIOCHEMICAL SCIENCES

The novel TRAIL-receptor agonist APG350 exerts superior therapeutic activity in pancreatic cancer cells

(2018) Karen Legler et al.   Cell Death & Disease

BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines

(2018) Delphine Merino et al.   CANCER CELL

The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2

(2017) Torsten Hartwig et al.   MOLECULAR CELL

Caspase-8 Acts in a Non-enzymatic Role as a Scaffold for Assembly of a Pro-inflammatory “FADDosome” Complex upon TRAIL Stimulation

(2017) Conor M. Henry et al.   MOLECULAR CELL

Caspase-10 Negatively Regulates Caspase-8-Mediated Cell Death, Switching the Response to CD95L in Favor of NF-κB Activation and Cell Survival

(2017) Sebastian Horn et al.   Cell Reports

TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis

(2017) Harsimran D. Singh et al.   Scientific Reports

Improvement of Pharmacokinetic Profile of TRAIL via Trimer-Tag Enhances its Antitumor Activity in vivo

(2017) Haipeng Liu et al.   Scientific Reports

Onto better TRAILs for cancer treatment

(2016) D de Miguel et al.   CELL DEATH AND DIFFERENTIATION

Co-operative and Hierarchical Binding of c-FLIP and Caspase-8: A Unified Model Defines How c-FLIP Isoforms Differentially Control Cell Fate

(2016) Michelle A. Hughes et al.   MOLECULAR CELL

Cancer Cell-Autonomous TRAIL-R Signaling Promotes KRAS-Driven Cancer Progression, Invasion, and Metastasis

(2015) Silvia von Karstedt et al.   CANCER CELL

Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic Nanobody® targeting the DR5 receptor

(2015) Kyriakos P. Papadopoulos et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity

(2015) Michael S. Rooney et al.   CELL

Targeting cancer with kinase inhibitors

(2015) Stefan Gross et al.   JOURNAL OF CLINICAL INVESTIGATION

Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display

(2015) Pradeep M. Nair et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Apo2L/TRAIL and the Death Receptor 5 Agonist Antibody AMG 655 Cooperate to Promote Receptor Clustering and Antitumor Activity

(2014) Jonathan D. Graves et al.   CANCER CELL

RIPK1 Blocks Early Postnatal Lethality Mediated by Caspase-8 and RIPK3

(2014) Christopher P. Dillon et al.   CELL

Getting TRAIL back on track for cancer therapy

(2014) J Lemke et al.   CELL DEATH AND DIFFERENTIATION

Regulated necrosis: the expanding network of non-apoptotic cell death pathways

(2014) Tom Vanden Berghe et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

TRAIL-R2-specific antibodies and recombinant TRAIL can synergise to kill cancer cells

(2014) M H Tuthill et al.   ONCOGENE

Systemic but not topical TRAIL-expressing mesenchymal stem cells reduce tumour growth in malignant mesothelioma

(2014) Elizabeth K Sage et al.   THORAX

Compartmentalization of TNF-related apoptosis-inducing ligand (TRAIL) death receptor functions: emerging role of nuclear TRAIL-R2

(2014) U Bertsch et al.   Cell Death & Disease

Selective CDK9 inhibition overcomes TRAIL resistance by concomitant suppression of cFlip and Mcl-1

(2013) J Lemke et al.   CELL DEATH AND DIFFERENTIATION

Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family

(2013) K Azijli et al.   CELL DEATH AND DIFFERENTIATION

Nuclear Death Receptor TRAIL-R2 Inhibits Maturation of Let-7 and Promotes Proliferation of Pancreatic and Other Tumor Cells

(2013) Verena Haselmann et al.   GASTROENTEROLOGY

The Pseudokinase MLKL Mediates Necroptosis via a Molecular Switch Mechanism

(2013) James M. Murphy et al.   IMMUNITY

APG350 Induces Superior Clustering of TRAIL Receptors and Shows Therapeutic Antitumor Efficacy Independent of Cross-Linking via Fc  Receptors

(2013) C. Gieffers et al.   MOLECULAR CANCER THERAPEUTICS

Liposomes Decorated with Apo2L/TRAIL Overcome Chemoresistance of Human Hematologic Tumor Cells

(2013) Diego De Miguel et al.   MOLECULAR PHARMACEUTICS

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

(2013) Andrew J Souers et al.   NATURE MEDICINE

Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death

(2013) Dimitry Ofengeim et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Inhibitor of Apoptosis (IAP) Proteins-Modulators of Cell Death and Inflammation

(2013) J. Silke et al.   Cold Spring Harbor Perspectives in Biology

Macrophage-expressed IFN-β Contributes to Apoptotic Alveolar Epithelial Cell Injury in Severe Influenza Virus Pneumonia

(2013) Katrin Högner et al.   PLoS Pathogens

Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase

(2012) Liming Sun et al.   CELL

Bortezomib and TRAIL: A perfect match for apoptotic elimination of tumour cells?

(2012) L.H.A.M. de Wilt et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Death Receptor 5 Networks That Are Highly Organized

(2012) Christopher C. Valley et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Death Effector Domain Chain DISC Model Reveals a Crucial Role for Caspase-8 Chain Assembly in Mediating Apoptotic Cell Death

(2012) Laura S. Dickens et al.   MOLECULAR CELL

TRAF2 Sets a Threshold for Extrinsic Apoptosis by Tagging Caspase-8 with a Ubiquitin Shutoff Timer

(2012) Francois Gonzalvez et al.   MOLECULAR CELL

Targeting IAP proteins for therapeutic intervention in cancer

(2012) Simone Fulda et al.   NATURE REVIEWS DRUG DISCOVERY

Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis

(2012) J. Zhao et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

ABT-737 promotes tBid mitochondrial accumulation to enhance TRAIL-induced apoptosis in glioblastoma cells

(2012) S Cristofanon et al.   Cell Death & Disease

Survival Function of the FADD-CASPASE-8-cFLIPL Complex

(2012) Christopher P. Dillon et al.   Cell Reports

Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands

(2012) Stephan Munich et al.   OncoImmunology

ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein

(2011) Guan Wang et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

(Un)expected roles of c-IAPs in apoptotic and NFκB signaling pathways

(2011) Eugene Varfolomeev et al.   CELL CYCLE

Targeting Aberrant PI3K/Akt Activation by PI103 Restores Sensitivity to TRAIL-Induced Apoptosis in Neuroblastoma

(2011) D. Opel et al.   CLINICAL CANCER RESEARCH

cIAPs Block Ripoptosome Formation, a RIP1/Caspase-8 Containing Intracellular Cell Death Complex Differentially Regulated by cFLIP Isoforms

(2011) Maria Feoktistova et al.   MOLECULAR CELL

RIP3 mediates the embryonic lethality of caspase-8-deficient mice

(2011) William J. Kaiser et al.   NATURE

Catalytic activity of the caspase-8–FLIPL complex inhibits RIPK3-dependent necrosis

(2011) Andrew Oberst et al.   NATURE

Functional complementation between FADD and RIP1 in embryos and lymphocytes

(2011) Haibing Zhang et al.   NATURE

A Dual PI3K/mTOR Inhibitor, PI-103, Cooperates with Stem Cell-Delivered TRAIL in Experimental Glioma Models

(2010) T. Bagci-Onder et al.   CANCER RESEARCH

Selective involvement of BH3-only proteins and differential targets of Noxa in diverse apoptotic pathways

(2010) L Zhang et al.   CELL DEATH AND DIFFERENTIATION

Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation

(2010) M Ehrenschwender et al.   CELL DEATH AND DIFFERENTIATION

BID is cleaved by caspase-8 within a native complex on the mitochondrial membrane

(2010) Z T Schug et al.   CELL DEATH AND DIFFERENTIATION

Tumor necrosis factor-mediated cell death: to break or to burst, that’s the question

(2010) Franky Van Herreweghe et al.   CELLULAR AND MOLECULAR LIFE SCIENCES

TRAIL-Induced Apoptosis Is Preferentially Mediated via TRAIL Receptor 1 in Pancreatic Carcinoma Cells and Profoundly Enhanced by XIAP Inhibitors

(2010) D. Stadel et al.   CLINICAL CANCER RESEARCH

Inducible Dimerization and Inducible Cleavage Reveal a Requirement for Both Processes in Caspase-8 Activation

(2010) Andrew Oberst et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5

(2010) Johannes Lemke et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

Molecular mechanisms of necroptosis: an ordered cellular explosion

(2010) Peter Vandenabeele et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

The inhibition of Bid expression by Akt leads to resistance to TRAIL-induced apoptosis in ovarian cancer cells

(2010) N Goncharenko-Khaider et al.   ONCOGENE

Potential Role of Soluble TRAIL in Epithelial Injury in Children with Severe RSV Infection

(2009) Reinout A. Bem et al.   AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY

Cullin3-Based Polyubiquitination and p62-Dependent Aggregation of Caspase-8 Mediate Extrinsic Apoptosis Signaling

(2009) Zhaoyu Jin et al.   CELL

Following TRAIL’s path in the immune system

(2009) Christina Falschlehner et al.   IMMUNOLOGY

The E3 Ubiquitin Ligase cIAP1 Binds and Ubiquitinates Caspase-3 and -7 via Unique Mechanisms at Distinct Steps in Their Processing

(2009) Young Eun Choi et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Bortezomib sensitizes primary human esthesioneuroblastoma cells to TRAIL-induced apoptosis

(2009) Ronald Koschny et al.   JOURNAL OF NEURO-ONCOLOGY

Mapatumumab and lexatumumab induce apoptosis in TRAIL-R1 and TRAIL-R2 antibody-resistant NSCLC cell lines when treated in combination with bortezomib

(2009) T. A. Luster et al.   MOLECULAR CANCER THERAPEUTICS

Reconstitution of the Death-Inducing Signaling Complex Reveals a Substrate Switch that Determines CD95-Mediated Death or Survival

(2009) Michelle A. Hughes et al.   MOLECULAR CELL

XIAP discriminates between type I and type II FAS-induced apoptosis

(2009) Philipp J. Jost et al.   NATURE

Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis

(2009) Sabrina L. Spencer et al.   NATURE

Membrane-bound Fas ligand only is essential for Fas-induced apoptosis

(2009) Lorraine A. O’ Reilly et al.   NATURE

BH3 Mimetic ABT-737 Potentiates TRAIL-Mediated Apoptotic Signaling by Unsequestering Bim and Bak in Human Pancreatic Cancer Cells

(2008) S. Huang et al.   CANCER RESEARCH

TNF-related apoptosis-inducing ligand: Signalling of a ‘smart’ molecule

(2008) Fabio Manzo et al.   INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY

TRAIL-R deficiency in mice enhances lymph node metastasis without affecting primary tumor development

(2008) Anne Grosse-Wilde et al.   JOURNAL OF CLINICAL INVESTIGATION

Identification of RIP1 kinase as a specific cellular target of necrostatins

(2008) Alexei Degterev et al.   Nature Chemical Biology

Evaluation of bronchoalveolar lavage fluid from ARDS patients with regard to apoptosis

(2007) Keu Sung Lee et al.   RESPIRATORY MEDICINE