Evidence map›Paper›PMID 34580712›Full record

ArticleDisease models & mechanisms2022

Pharmacological or genetic inhibition of hypoxia signaling attenuates oncogenic RAS-induced cancer phenotypes.

Jun-Yi Zhu, Xiaohu Huang, Yulong Fu, Yin Wang, Pan Zheng, Yang Liu, Zhe Han

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

Article in Disease models & mechanisms, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 42% 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

5 citing papers in PubMed, 6 citations in OpenAlex.

  1. The Roles of Histone Lysine Methyltransferases in Heart Development and Disease.Journal of cardiovascular development and disease · 2023
    Review
  2. Hypoxia in Skin Cancer: Molecular Basis and Clinical Implications.International journal of molecular sciences · 2023
    Review
  3. First person - Jun-yi Zhu and Xiaohu Huang.Disease models & mechanisms · 2022
    Article
  4. Article
  5. UsingFrontiers in cell and developmental biology · 2022
    Review
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

7 authors at 1 institution in 1 country.

Jun-Yi ZhuCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-4517-101X
Xiaohu HuangCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0003-4580-4582
Yulong FuCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0001-7991-9965
Yin WangDivision of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Pan ZhengDivision of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Yang LiuDivision of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Zhe HanCenter for Precision Disease Modeling, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.ORCID 0000-0002-5177-7798
University of Maryland, Baltimore · US

Funding

Checkpoints of Host Response to Cellular InjuriesR01AI064350 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, YANG, ZHENG, PAN · 2006 to 2019
$5.6M
Modeling Nephrotic Syndrome in Drosophila NephrocytesR01DK098410 · NIDDK · UNIVERSITY OF MARYLAND BALTIMORE · PI HAN, ZHE · 2014 to 2022
$3.3M
INCLUDE19-Ancestral roles of histone-modifying genes in heart development and diseaseR01HL134940 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI HAN, ZHE · 2017 to 2020
$2.4M
NHLBI NIH HHS R01 HL134940NIAID NIH HHS R01 AI064350NIDDK NIH HHS R01 DK098410
6 · The paper itself

Abstract

Oncogenic Ras mutations are highly prevalent in hematopoietic malignancies. However, it is difficult to directly target oncogenic RAS proteins for therapeutic intervention. We have developed a Drosophila acute myeloid leukemia model induced by human KRASG12V, which exhibits a dramatic increase in myeloid-like leukemia cells. We performed both genetic and drug screens using this model. The genetic screen identified 24 candidate genes able to attenuate the oncogenic RAS-induced phenotype, including two key hypoxia pathway genes HIF1A and ARNT (HIF1B). The drug screen revealed that echinomycin, an inhibitor of HIF1A, can effectively attenuate the leukemia phenotype caused by KRASG12V. Furthermore, we showed that echinomycin treatment can effectively suppress oncogenic RAS-driven leukemia cell proliferation, using both human leukemia cell lines and a mouse xenograft model. These data suggest that inhibiting the hypoxia pathway could be an effective treatment approach and that echinomycin is a promising targeted drug to attenuate oncogenic RAS-induced cancer phenotypes. This article has an associated First Person interview with the first author of the paper.

Indexed as

EchinomycinLeukemia, Myeloid, AcuteAnimalsGenes, rasHumansHypoxiaMicePhenotypeEchinomycinDrosophilaEchinomycinHIF1AHypoxia pathwayLeukemiaMouse xenograftsOncogenic RAS

Identifiers

PMID34580712
PMCPMC8617310
OpenAlexW3202392192

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.