Evidence map›Paper›PMID 28869602›Full record

ArticleOncogene2018

Targeting mitochondrial translation by inhibiting DDX3: a novel radiosensitization strategy for cancer treatment.

M R Heerma van Voss, F Vesuna, G M Bol, J Afzal, S Tantravedi, Y Bergman, K Kammers, M Lehar, R Malek, M Ballew and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
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  6. AnBioengineering & translational medicine · 2025
    Article
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  18. Article
  19. A Dual Role of DDX3X in dsRNA-Derived Innate Immune Signaling.Frontiers in molecular biosciences · 2022
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 2 institutions in 2 countries.

M R Heerma van VossDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
F VesunaDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.ORCID 0000-0002-0356-5096
G M BolDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
J AfzalDepartment of Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
S TantravediDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Y BergmanDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
K KammersDepartment of Biostatistics, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
M LeharDepartment of Otolaryngology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
R MalekDepartment of Radiation Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
M BallewDepartment of Radiation Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
N Ter HoeveDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
D AbouDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
D ThorekDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
C BerlinickeWilmer Eye Institute, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
M YazdankhahWilmer Eye Institute, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
D SinhaWilmer Eye Institute, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
A LeDepartment of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
R AbrahamsDepartment of Cardiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
P T TranDepartment of Radiation Oncology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
P J van DiestDepartment of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
V RamanDepartment of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Johns Hopkins University · USUniversity Medical Center Utrecht · NL

Funding

Glutaminase Inhibitor Drug Discovery and Nanoparticle-Based Delivery for Pancreatic Cancer TherapyR01CA193895 · NCI · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S., LE, ANNE · 2016 to 2020
$2.1M
Structure-Functions Studies of Twist1-induced Radioresistance in Lung CancerR01CA166348 · NCI · JOHNS HOPKINS UNIVERSITY · PI TRAN, PHUOC T. · 2013 to 2017
$1.7M
Functional Imaging of Twist induced breast cancerR01CA140226 · NCI · JOHNS HOPKINS UNIVERSITY · PI RAMAN, VENU · 2010 to 2014
$1.6M
The role of Twist in inducing breast cancer initiating cells and metastasisR01CA131250 · NCI · JOHNS HOPKINS UNIVERSITY · PI RAMAN, VENU · 2011 to 2015
$1.2M
NCI NIH HHS R01 CA131250NCI NIH HHS R01 CA140226NCI NIH HHS R01 CA166348NCI NIH HHS R01 CA193895
6 · The paper itself

Abstract

DDX3 is a DEAD box RNA helicase with oncogenic properties. RK-33 is developed as a small-molecule inhibitor of DDX3 and showed potent radiosensitizing activity in preclinical tumor models. This study aimed to assess DDX3 as a target in breast cancer and to elucidate how RK-33 exerts its anti-neoplastic effects. High DDX3 expression was present in 35% of breast cancer patient samples and correlated with markers of aggressiveness and shorter survival. With a quantitative proteomics approach, we identified proteins involved in the mitochondrial translation and respiratory electron transport pathways to be significantly downregulated after RK-33 or DDX3 knockdown. DDX3 localized to the mitochondria and DDX3 inhibition with RK-33 reduced mitochondrial translation. As a consequence, oxygen consumption rates and intracellular ATP concentrations decreased and reactive oxygen species (ROS) increased. RK-33 antagonized the increase in oxygen consumption and ATP production observed after exposure to ionizing radiation and reduced DNA repair. Overall, we conclude that DDX3 inhibition with RK-33 causes radiosensitization in breast cancer through inhibition of mitochondrial translation, which results in reduced oxidative phosphorylation capacity and increased ROS levels, culminating in a bioenergetic catastrophe.

Indexed as

AzepinesBreastBreast NeoplasmsCell Line, TumorDEAD-box RNA HelicasesDown-RegulationFemaleGene Knockdown TechniquesHumansImidazolesMitochondriaOncogenesProtein BiosynthesisProteomicsRadiation-Sensitizing AgentsReactive Oxygen Species3,7-dihydro-3,7-bis((4-methoxyphenyl)methyl)-2H-diimidazo(4,5-d:4',5'-f)(1,3)diazepin-2-oneAzepinesDDX3X protein, humanDEAD-box RNA HelicasesImidazolesRadiation-Sensitizing AgentsReactive Oxygen Species

Identifiers

PMID28869602
PMCPMC5756132
OpenAlexW2751349734

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.