Evidence map›Paper›PMID 28978636›Full record

ArticleCancer research2017

EZH2 Modifies Sunitinib Resistance in Renal Cell Carcinoma by Kinome Reprogramming.

Remi Adelaiye-Ogala, Justin Budka, Nur P Damayanti, Justine Arrington, Mary Ferris, Chuan-Chih Hsu, Sreenivasulu Chintala, Ashley Orillion, Kiersten Marie Miles, Li Shen and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
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

63 citing papers in PubMed.

  1. Review
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  5. Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024
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3 more citing papers are in PubMed but not listed here.

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

29 authors.

Remi Adelaiye-OgalaDepartment of Cancer Pathology and Prevention, University at Buffalo, Buffalo, New York.
Justin BudkaMedical Sciences, Indiana University, Bloomington, Indiana.
Nur P DamayantiDepartment of Biomedical Engineering, Purdue University, West Lafayette, Indiana.
Justine ArringtonDepartment of Biochemistry, Purdue University, West Lafayette, Indiana.
Mary FerrisMedical Sciences, Indiana University, Bloomington, Indiana.
Chuan-Chih HsuDepartment of Biochemistry, Purdue University, West Lafayette, Indiana.
Sreenivasulu ChintalaDepartment of Medicine, Indiana University, Indianapolis, Indiana.
Ashley OrillionDepartment of Pharmacology and Toxicology, Indiana University, Indianapolis, Indiana.
Kiersten Marie MilesCenter for Personalized Medicine, Roswell Park Cancer Institute, New York, New York.
Li ShenDepartment of Medicine, Roswell Park Cancer Institute, New York, New York.
May ElbannaDepartment of Pharmacology and Toxicology, Indiana University, Indianapolis, Indiana.
Eric CiamporceroDepartment of Medicine and Experimental Oncology, University of Turin, Turin, Italy.
Sreevani ArisaDepartment of Medicine, Indiana University, Indianapolis, Indiana.
Piergiorgio PettazzoniDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Giulio F DraettaDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mukund SeshadriDepartment of Pharmacology and Therapeutics, Roswell Park Cancer Institute, New York, New York.
Bradley HancockDepartment of Surgery, Indiana University, Indianapolis, Indiana.
Milan RadovichDepartment of Surgery, Indiana University, Indianapolis, Indiana.
Janaiah KotaDepartment of Medical and Molecular Genetics, Indiana University, Indianapolis, Indiana.
Michael BuckCenter of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, New York.
Heike KeilhackEpizyme Inc., Cambridge, Massachusetts.
Brian P McCarthyDepartment of Radiology and Imaging Sciences, Indiana University, Indianapolis, Indiana.
Scott A PersohnDepartment of Radiology and Imaging Sciences, Indiana University, Indianapolis, Indiana.
Paul R TerritoDepartment of Radiology and Imaging Sciences, Indiana University, Indianapolis, Indiana.
Yong ZangDepartment of Biostatistics, Indiana University, Indianapolis, Indiana.
Joseph IrudayarajMedical Sciences, Indiana University, Bloomington, Indiana.
W Andy TaoDepartment of Biochemistry, Purdue University, West Lafayette, Indiana.
Peter HollenhorstMedical Sciences, Indiana University, Bloomington, Indiana. pchollen@indiana.edu rpili@iu.edu.
Roberto PiliDepartment of Cancer Pathology and Prevention, University at Buffalo, Buffalo, New York. pchollen@indiana.edu rpili@iu.edu.

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Christine B. Ambrosone · 1985 to 2026
$116.6M
EXTRAMURAL RESEARCH FACILITIES IMPROVEMENT: NEUROLOGICAL DISORDERS:ALZ, PDC06RR020128 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI FIFE, ROSE S · 2004 to 2004
$3.7M
Targeting HIF-1alpha in renal cell carcinoma: the role of HDAC inhibitorsR01CA135321 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI PILI, ROBERTO · 2008 to 2010
$1.0M
NCI NIH HHS P30 CA016056NCI NIH HHS R01 CA135321NCRR NIH HHS C06 RR020128
6 · The paper itself

Abstract

Acquired and intrinsic resistance to receptor tyrosine kinase inhibitors (RTKi) represents a major hurdle in improving the management of clear cell renal cell carcinoma (ccRCC). Recent reports suggest that drug resistance is driven by tumor adaptation via epigenetic mechanisms that activate alternative survival pathways. The histone methyl transferase EZH2 is frequently altered in many cancers, including ccRCC. To evaluate its role in ccRCC resistance to RTKi, we established and characterized a spontaneously metastatic, patient-derived xenograft model that is intrinsically resistant to the RTKi sunitinib, but not to the VEGF therapeutic antibody bevacizumab. Sunitinib maintained its antiangiogenic and antimetastatic activity but lost its direct antitumor effects due to kinome reprogramming, which resulted in suppression of proapoptotic and cell-cycle-regulatory target genes. Modulating EZH2 expression or activity suppressed phosphorylation of certain RTKs, restoring the antitumor effects of sunitinib in models of acquired or intrinsically resistant ccRCC. Overall, our results highlight EZH2 as a rational target for therapeutic intervention in sunitinib-resistant ccRCC as well as a predictive marker for RTKi response in this disease.

Indexed as

AnimalsAntineoplastic AgentsBevacizumabCarcinoma, Renal CellCell Line, TumorDrug Resistance, NeoplasmEnhancer of Zeste Homolog 2 ProteinFemaleHumansIndolesKidney NeoplasmsLung NeoplasmsMiceMice, Inbred ICRMice, SCIDNeovascularization, PathologicAntineoplastic AgentsBevacizumabEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanIndolesPyrrolesReceptor Protein-Tyrosine KinasesSunitinibVascular Endothelial Growth Factor AVEGFA protein, human

Identifiers

PMID28978636
PMCPMC5712262

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Registered trials

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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.