Evidence map›Paper›PMID 30723171›Full record

ArticleScience signaling2019

Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition.

Arnaud Augert, Emily Eastwood, Ali H Ibrahim, Nan Wu, Eli Grunblatt, Ryan Basom, Denny Liggitt, Keith D Eaton, Renato Martins, John T Poirier and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Science signaling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 1 pooled it
11.3field-weighted citation impact, top 1% 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

149 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026
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  6. Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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89 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

15 authors at 6 institutions in 3 countries.

Arnaud AugertDivisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.ORCID 0000-0003-0636-3024
Emily EastwoodDivisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.ORCID 0000-0002-8329-2090
Ali H IbrahimDivisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.ORCID 0000-0002-9276-0335
Nan WuDivisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.
Eli GrunblattDivisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.
Ryan BasomGenomics and Bioinformatics Shared Resource, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.ORCID 0000-0001-6137-1807
Denny LiggittDepartment of Comparative Medicine, University of Washington, Seattle, WA 98195, USA.
Keith D EatonDivision of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.ORCID 0000-0001-5025-2001
Renato MartinsDivision of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA 98109, USA.
John T PoirierDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0001-9795-5644
Charles M RudinDepartment of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0001-5204-3465
Francesca MillettiPharmaceutical Research and Early Development, Roche Innovation Center, New York, NY 10016, USA.
Wei-Yi ChengPharmaceutical Research and Early Development, Roche Innovation Center, New York, NY 10016, USA.ORCID 0000-0002-7588-298X
Fiona MackPharmaceutical Research and Early Development, Roche Innovation Center, New York, NY 10016, USA.
David MacPhersonDivisions of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA. dmacpher@fredhutch.org.ORCID 0000-0003-3729-907X
Fred Hutch Cancer Center · USRoche (Switzerland) · CHMemorial Sloan Kettering Cancer Center · USUniversity of Washington · USUniversity of Washington Medical Center · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Marian Esvelt · 1985 to 2026
$296.4M
University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Interdisciplinary Tranining in Cancer ResearchT32CA080416 · NCI · UNIVERSITY OF WASHINGTON · PI STODDARD, BARRY L. · 1998 to 2023
$9.7M
Chromosome Metabolism and Cancer Training GrantT32CA009657 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI EISENMAN, ROBERT NEIL · 1991 to 2020
$7.6M
Investigating CREBBP as a tumor suppressor in small cell lung cancerR01CA200547 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MACPHERSON, DAVID · 2017 to 2021
$2.2M
Interrogation of MLL2 as a tumor suppressor gene in lung cancerR01CA181449 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI MACPHERSON, DAVID · 2015 to 2019
$2.0M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA015704NCI NIH HHS R01 CA181449NCI NIH HHS R01 CA200547NCI NIH HHS T32 CA009657NCI NIH HHS T32 CA080416NIGMS NIH HHS T32 GM007266
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) is a recalcitrant, aggressive neuroendocrine-type cancer for which little change to first-line standard-of-care treatment has occurred within the last few decades. Unlike nonsmall cell lung cancer (NSCLC), SCLC harbors few actionable mutations for therapeutic intervention. Lysine-specific histone demethylase 1A (LSD1 also known as KDM1A) inhibitors were previously shown to have selective activity in SCLC models, but the underlying mechanism was elusive. Here, we found that exposure to the selective LSD1 inhibitor ORY-1001 activated the NOTCH pathway, resulting in the suppression of the transcription factor ASCL1 and the repression of SCLC tumorigenesis. Our analyses revealed that LSD1 bound to the

Indexed as

Xenograft Model Antitumor AssaysAnimalsBasic Helix-Loop-Helix ProteinsCell Line, TumorEnzyme InhibitorsGene Expression Regulation, NeoplasticHistone DemethylasesHumansKaplan-Meier EstimateLung NeoplasmsMice, Inbred NODMice, KnockoutMice, SCIDReceptors, NotchSignal TransductionSmall Cell Lung CarcinomaASCL1 protein, humanBasic Helix-Loop-Helix ProteinsEnzyme InhibitorsHistone DemethylasesKDM1A protein, humanReceptors, Notch

Identifiers

PMID30723171
PMCPMC6530478
OpenAlexW2913103186

What OpenQuestion holds

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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.