Targeting Cullin-RING E3 Ligases for Radiosensitization: From NEDDylation Inhibition to PROTACs

Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders

(2020) Meng Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

NEDD8 nucleates a multivalent cullin–RING–UBE2D ubiquitin ligation assembly

(2020) Kheewoong Baek et al.   NATURE

Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers

(2020) Amy M. Buckley et al.   Nature Reviews Gastroenterology & Hepatology

Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment

(2020) Steven Kregel et al.   NEOPLASIA

Light-induced control of protein destruction by opto-PROTAC

(2020) Jing Liu et al.   Science Advances

PHOTACs enable optical control of protein degradation

(2020) Martin Reynders et al.   Science Advances

Discovery of ERD-308 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Estrogen Receptor (ER)

(2019) Jiantao Hu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer

(2019) Xin Han et al.   JOURNAL OF MEDICINAL CHEMISTRY

FBXW7 in Cancer: What Has Been Unraveled Thus Far?

(2019) Bethsebie Lalduhsaki Sailo et al.   Cancers

Preclinical study using androgen receptor (AR) degradation enhancer to increase radiotherapy efficacy via targeting radiation-increased AR to better suppress prostate cancer progression

(2019) Fu-Ju Chou et al.   EBioMedicine

Chemotherapy and Radiation Versus Chemotherapy Alone for Elderly Patients With N3 Stage IIIB NSCLC

(2019) Angel Qin et al.   Clinical Lung Cancer

TAS4464, a highly potent and selective inhibitor of NEDD8 activating enzyme, suppresses neddylation and shows antitumor activity in diverse cancer models

(2019) Chihoko Yoshimura et al.   MOLECULAR CANCER THERAPEUTICS

The ubiquitin–proteasome system in kidney physiology and disease

(2019) Catherine Meyer-Schwesinger   Nature Reviews Nephrology

Effects of Neddylation and mTOR Inhibition in Acute Myelogenous Leukemia

(2019) Naxin Guo et al.   Translational Oncology

Targeted protein degradation: elements of PROTAC design

(2019) Stacey-Lynn Paiva et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

PROTAC moves in on lymphoma

(2019) Megan Cully   NATURE REVIEWS DRUG DISCOVERY

Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: Preliminary assessment of toxicity

(2019) Edy Ippolito et al.   BREAST

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders

(2019) Shang Su et al.   JOURNAL OF MEDICINAL CHEMISTRY

Toxicity of locoregional radiotherapy in combination with bevacizumab in patients with non-metastatic breast cancer (TOLERAB): Final long-term evaluation

(2019) Alice Clément-Zhao et al.   PLoS One

Cullin Ring Ubiquitin Ligases (CRLs) in Cancer: Responses to Ionizing Radiation (IR) Treatment

(2019) Shahd Fouad et al.   Frontiers in Physiology

Anticancer drug discovery by targeting cullin neddylation

(2019) Qing Yu et al.   Acta Pharmaceutica Sinica B

Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor κB pathways

(2019) Hiromi Muraoka et al.   CANCER SCIENCE

Discovery of a First-in-Class Mitogen-Activated Protein Kinase Kinase 1/2 Degrader

(2019) Jieli Wei et al.   JOURNAL OF MEDICINAL CHEMISTRY

Aggregation of lipid rafts activates c-met and c-Src in non-small cell lung cancer cells

(2018) Juan Zeng et al.   BMC CANCER

Protein neddylation and its alterations in human cancers for targeted therapy

(2018) Lisha Zhou et al.   CELLULAR SIGNALLING

p16(INK4a) status and survival benefit of EGFR inhibitors in head and neck squamous cell cancer: A systematic review and meta-analysis

(2018) Yapin Su et al.   CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

Estrogen Receptor Signaling in Radiotherapy: From Molecular Mechanisms to Clinical Studies

(2018) Chao Rong et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Phase 2 Study of Bortezomib Combined With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

(2018) Xiao-Tang Kong et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK)

(2018) Chelsea E. Powell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Functional TRIM24 degrader via conjugation of ineffectual bromodomain and VHL ligands

(2018) Lara N. Gechijian et al.   Nature Chemical Biology

Kinase inhibitors: the road ahead

(2018) Fleur M. Ferguson et al.   NATURE REVIEWS DRUG DISCOVERY

Cancer Radiosensitizers

(2018) Hao Wang et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Bruton's Tyrosine Kinase degradation as a therapeutic strategy for cancer

(2018) Dennis Dobrovolsky et al.   BLOOD

Crosstalk between Phosphoinositide 3-kinase/Akt signaling pathway with DNA damage response and oxidative stress in cancer

(2018) Ansar Karimian et al.   JOURNAL OF CELLULAR BIOCHEMISTRY

Phase 1 Trial of Everolimus and Radiation Therapy for Salvage Treatment of Biochemical Recurrence in Prostate Cancer Patients Following Prostatectomy

(2017) Vivek Narayan et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

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

The Neddylation Inhibitor Pevonedistat (MLN4924) Suppresses and Radiosensitizes Head and Neck Squamous Carcinoma Cells and Tumors

(2017) Vanessa Vanderdys et al.   MOLECULAR CANCER THERAPEUTICS

EGFR heterogeneity and implications for therapeutic intervention in glioblastoma

(2017) Eskil Eskilsson et al.   NEURO-ONCOLOGY

A randomized phase II study of everolimus in combination with chemoradiation in newly diagnosed glioblastoma: results of NRG Oncology RTOG 0913

(2017) Prakash Chinnaiyan et al.   NEURO-ONCOLOGY

Taxane-mediated radiosensitization derives from chromosomal missegregation on tripolar mitotic spindles orchestrated by AURKA and TPX2

(2017) M Orth et al.   ONCOGENE

Inhibition of the NEDD8 conjugation pathway induces calcium-dependent compensatory activation of the pro-survival MEK/ERK pathway in acute lymphoblastic leukemia

(2017) Shuhua Zheng et al.   Oncotarget

The Role of NF-κB Inhibitors in Cell Response to Radiation

(2016) Sajjad Molavi Pordanjani et al.   CURRENT MEDICINAL CHEMISTRY

Avoiding Severe Toxicity From Combined BRAF Inhibitor and Radiation Treatment: Consensus Guidelines from the Eastern Cooperative Oncology Group (ECOG)

(2016) Christopher J. Anker et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

Carbon Ion Radiation Therapy for Unresectable Sacral Chordoma: An Analysis of 188 Cases

(2016) Reiko Imai et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

The NEDD8-activating enzyme inhibitor pevonedistat activates the eIF2α and mTOR pathways inducing UPR-mediated cell death in acute lymphoblastic leukemia

(2016) Gilles M. Leclerc et al.   LEUKEMIA RESEARCH

Radiosensitization of Human Colorectal Cancer Cells by MLN4924

(2016) Juefeng Wan et al.   TECHNOLOGY IN CANCER RESEARCH & TREATMENT

The structure and regulation of Cullin 2 based E3 ubiquitin ligases and their biological functions

(2016) Weijia Cai et al.   Cell Division

Radiosensitization by the investigational NEDD8-activating enzyme inhibitor MLN4924 (pevonedistat) in hormone-resistant prostate cancer cells

(2016) Xiaofang Wang et al.   Oncotarget

Antihormonal agents as a strategy to improve the effect of chemo-radiation in cervical cancer: in vitro and in vivo study

(2015) Mariana Segovia-Mendoza et al.   BMC CANCER

MEK inhibitor GSK1120212-mediated radiosensitization of pancreatic cancer cells involves inhibition of DNA double-strand break repair pathways

(2015) Adriana Estrada-Bernal et al.   CELL CYCLE

Molecular Pathways: A Novel Approach to Targeting Hypoxia and Improving Radiotherapy Efficacy via Reduction in Oxygen Demand

(2015) A. Lin et al.   CLINICAL CANCER RESEARCH

Molecular Pathways: Overcoming Radiation Resistance by Targeting DNA Damage Response Pathways

(2015) M. A. Morgan et al.   CLINICAL CANCER RESEARCH

Phase I Study of the Novel Investigational NEDD8-Activating Enzyme Inhibitor Pevonedistat (MLN4924) in Patients with Relapsed/Refractory Multiple Myeloma or Lymphoma

(2015) J. J. Shah et al.   CLINICAL CANCER RESEARCH

The Accomplices of NF-κB Lead to Radioresistance

(2015) Miaomiao Bai et al.   CURRENT PROTEIN & PEPTIDE SCIENCE

Inhibition of MEK confers hypersensitivity to X-radiation in the context of BRAF mutation in a model of childhood astrocytoma

(2015) Adam Studebaker et al.   PEDIATRIC BLOOD & CANCER

Targeting neddylation induces DNA damage and checkpoint activation and sensitizes chronic lymphocytic leukemia B cells to alkylating agents

(2015) C Paiva et al.   Cell Death & Disease

Induction of p21-Dependent Senescence by an NAE Inhibitor, MLN4924, as a Mechanism of Growth Suppression

(2015) Lijun Jia et al.   NEOPLASIA

MLN4924, an NAE inhibitor, suppresses AKT and mTOR signaling via upregulation of REDD1 in human myeloma cells

(2014) Y. Gu et al.   BLOOD

The Nedd8-Activating Enzyme Inhibitor MLN4924 Thwarts Microenvironment-Driven NF- B Activation and Induces Apoptosis in Chronic Lymphocytic Leukemia B Cells

(2014) J. C. Godbersen et al.   CLINICAL CANCER RESEARCH

Radiation-induced signaling pathways that promote cancer cell survival (Review)

(2014) ASHLEY L. HEIN et al.   INTERNATIONAL JOURNAL OF ONCOLOGY

Radiosensitization of glioblastoma cells using a histone deacetylase inhibitor (SAHA) comparing carbon ions with X-rays

(2014) Lara Barazzuol et al.   INTERNATIONAL JOURNAL OF RADIATION BIOLOGY

Interaction of Radiation Therapy With Molecular Targeted Agents

(2014) Zachary S. Morris et al.   JOURNAL OF CLINICAL ONCOLOGY

Compliance and toxicity of the hypoxic radiosensitizer nimorazole in the treatment of patients with head and neck squamous cell carcinoma (HNSCC)

(2013) Mohamed A. Hassan Metwally et al.   ACTA ONCOLOGICA

A Phase I Study of Temsirolimus and Thoracic Radiation in Non–Small-Cell Lung Cancer

(2013) Saiama N. Waqar et al.   Clinical Lung Cancer

Cullin-RING Ligases as Attractive Anti-cancer Targets

(2013) Yongchao Zhao et al.   CURRENT PHARMACEUTICAL DESIGN

Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

(2013) LAURA ASTOLFI et al.   ONCOLOGY REPORTS

Concurrent whole brain radiotherapy and bortezomib for brain metastasis

(2013) Christopher D Lao et al.   Radiation Oncology

The ATM signaling network in development and disease

(2013) Travis H. Stracker et al.   Frontiers in Genetics

The p21-Dependent Radiosensitization of Human Breast Cancer Cells by MLN4924, an Investigational Inhibitor of NEDD8 Activating Enzyme

(2012) Dong Yang et al.   PLoS One

Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis

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

Radiosensitization of Human Pancreatic Cancer Cells by MLN4924, an Investigational NEDD8-Activating Enzyme Inhibitor

(2011) D. Wei et al.   CANCER RESEARCH

Early Tumor Progression Associated with Enhanced EGFR Signaling with Bortezomib, Cetuximab, and Radiotherapy for Head and Neck Cancer

(2011) A. Argiris et al.   CLINICAL CANCER RESEARCH

SCF E3 Ubiquitin Ligases as Anticancer Targets

(2011) L. Jia et al.   CURRENT CANCER DRUG TARGETS

DEPTOR, an mTOR Inhibitor, Is a Physiological Substrate of SCFβTrCP E3 Ubiquitin Ligase and Regulates Survival and Autophagy

(2011) Yongchao Zhao et al.   MOLECULAR CELL

Resistance to MEK Inhibitors: Should We Co-Target Upstream?

(2011) P. I. Poulikakos et al.   Science Signaling

Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia

(2010) R. T. Swords et al.   BLOOD

NEDD8-Targeting Drug MLN4924 Elicits DNA Rereplication by Stabilizing Cdt1 in S Phase, Triggering Checkpoint Activation, Apoptosis, and Senescence in Cancer Cells

(2010) J. J. Lin et al.   CANCER RESEARCH

Ubiquitylation and proteasomal degradation of the p21Cip1, p27Kip1and p57Kip2CDK inhibitors

(2010) Zhimin Lu et al.   CELL CYCLE

Disruption of Sag/Rbx2/Roc2 induces radiosensitization by increasing ROS levels and blocking NF-κB activation in mouse embryonic stem cells

(2010) Mingjia Tan et al.   FREE RADICAL BIOLOGY AND MEDICINE

Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

(2010) Thomas J. Pugh et al.   INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS

CRL4Cdt2 Regulates Cell Proliferation and Histone Gene Expression by Targeting PR-Set7/Set8 for Degradation

(2010) Tarek Abbas et al.   MOLECULAR CELL

E2-RING Expansion of the NEDD8 Cascade Confers Specificity to Cullin Modification

(2009) Danny T. Huang et al.   MOLECULAR CELL

The F Box Protein Fbx6 Regulates Chk1 Stability and Cellular Sensitivity to Replication Stress

(2009) You-Wei Zhang et al.   MOLECULAR CELL

An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer

(2009) Teresa A. Soucy et al.   NATURE

Structural Insights into NEDD8 Activation of Cullin-RING Ligases: Conformational Control of Conjugation

(2008) David M. Duda et al.   CELL

PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex

(2008) T. Abbas et al.   GENES & DEVELOPMENT

Multimodal Activation of the Ubiquitin Ligase SCF by Nedd8 Conjugation

(2008) Anjanabha Saha et al.   MOLECULAR CELL