Evidence map›Paper›PMID 30626880›Full record

ArticleNature communications2019

A chemical biology screen identifies a vulnerability of neuroendocrine cancer cells to SQLE inhibition.

Christopher E Mahoney, David Pirman, Victor Chubukov, Taryn Sleger, Sebastian Hayes, Zi Peng Fan, Eric L Allen, Ying Chen, Lingling Huang, Meina Liu and 19 more

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

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.7field-weighted citation impact, top 5% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Squalene Epoxidase: Its Regulations and Links with Cancers.International journal of molecular sciences · 2024
    Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Terbinafine prevents colorectal cancer growth by inducing dNTP starvation and reducing immune suppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  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

29 authors at 1 institution in 1 country.

Christopher E MahoneyAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-9480-5744
David PirmanAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Victor ChubukovAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Taryn SlegerAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Sebastian HayesAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0002-2383-9461
Zi Peng FanAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Eric L AllenAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Ying ChenShanghai ChemPartner Co. Ltd., 998 Halei Road, Pudong, 201203, Shanghai, China.
Lingling HuangShanghai ChemPartner Co. Ltd., 998 Halei Road, Pudong, 201203, Shanghai, China.
Meina LiuShanghai ChemPartner Co. Ltd., 998 Halei Road, Pudong, 201203, Shanghai, China.
Yingjia ZhangShanghai ChemPartner Co. Ltd., 998 Halei Road, Pudong, 201203, Shanghai, China.
Gabrielle McDonaldAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Rohini NarayanaswamyAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Sung ChoeAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Yue ChenAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Stefan GrossAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.ORCID http://orcid.org/0000-0003-4716-673X
Giovanni CianchettaAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Anil K PadyanaAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Stuart MurrayAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Wei LiuAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Kevin M MarksAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Joshua MurtieAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Marion DorschAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Shengfang JinAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Nelamangala NagarajaAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Scott A BillerAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Thomas RoddyAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Janeta Popovici-MullerAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA.
Gromoslaw A SmolenAgios Pharmaceuticals, 88 Sidney Street, Cambridge, MA, 02139, USA. gsmolen@celsiustx.com.ORCID http://orcid.org/0000-0003-0136-4685
Agios Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Aberrant metabolism of cancer cells is well appreciated, but the identification of cancer subsets with specific metabolic vulnerabilities remains challenging. We conducted a chemical biology screen and identified a subset of neuroendocrine tumors displaying a striking pattern of sensitivity to inhibition of the cholesterol biosynthetic pathway enzyme squalene epoxidase (SQLE). Using a variety of orthogonal approaches, we demonstrate that sensitivity to SQLE inhibition results not from cholesterol biosynthesis pathway inhibition, but rather surprisingly from the specific and toxic accumulation of the SQLE substrate, squalene. These findings highlight SQLE as a potential therapeutic target in a subset of neuroendocrine tumors, particularly small cell lung cancers.

Indexed as

Drug Delivery SystemsDrug Screening Assays, AntitumorAntineoplastic AgentsCell Line, TumorCholesterolGene DeletionGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansSqualene MonooxygenaseAntineoplastic AgentsCholesterolSqualene Monooxygenase

Identifiers

PMID30626880
PMCPMC6327044
OpenAlexW2913980917

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.