Evidence map›Paper›PMID 26980196›Full record

ArticleCancer biology & therapy2016

Ganetespib radiosensitization for liver cancer therapy.

Sivarajan T Chettiar, Reem Malek, Anvesh Annadanam, Katriana M Nugent, Yoshinori Kato, Hailun Wang, Jessica A Cades, Kekoa Taparra, Zineb Belcaid, Matthew Ballew and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer biology & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

7 citing papers in PubMed, 18 citations in OpenAlex.

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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

16 authors at 4 institutions in 1 country.

Sivarajan T Chettiara Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Reem Maleka Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Anvesh Annadanama Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Katriana M Nugenta Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Yoshinori Katob The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Hailun Wanga Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Jessica A Cadesa Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Kekoa Taparraa Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Zineb Belcaide Department of Neurosurgery , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Matthew Ballewa Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Sarah Manmillera Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
David Proiaf Synta Pharmaceuticals Corp. , Lexington , MD , USA.
Michael Limc Department of Oncology , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Robert A Andersg Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Joseph M Hermana Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Phuoc T Trana Department of Radiation Oncology and Molecular Radiation Sciences , Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine , Baltimore , MD , USA.
Johns Hopkins University · USSidney Kimmel Comprehensive Cancer Center · USJohns Hopkins Medicine · USSynta Pharmaceuticals (United States) · US

Funding

Structure-Functions Studies of Twist1-induced Radioresistance in Lung CancerR01CA166348 · NCI · JOHNS HOPKINS UNIVERSITY · PI TRAN, PHUOC T. · 2013 to 2017
$1.7M
Mechanisms of TWIST1-induced sorafenib resistance in liver CAF31CA189588 · NCI · JOHNS HOPKINS UNIVERSITY · PI TAPARRA, KEKOA · 2014 to 2015
$84k
NCI NIH HHS F31 CA189588NCI NIH HHS R01 CA166348
6 · The paper itself

Abstract

Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33-1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies.

Indexed as

Cell ProliferationHumansLiver NeoplasmsRadiation-Sensitizing AgentsSignal TransductionTriazolesRadiation-Sensitizing AgentsSTA 9090TriazolesG2-M arrestGanetespibHsp90liver cancerradiation therapyradiosensitizerstress response machinery

Identifiers

PMID26980196
PMCPMC4910914
OpenAlexW2300422020

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.