Evidence map›Paper›PMID 36509998›Full record

ArticleOncogene2023

Targeting PEA3 transcription factors to mitigate small cell lung cancer progression.

David W Shia, WooSuk Choi, Preethi Vijayaraj, Valarie Vuong, Jenna M Sandlin, Michelle M Lu, Adam Aziz, Caliope Marin, Cody J Aros, Chandani Sen and 6 more

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

Article in Oncogene, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.9field-weighted citation impact, top 12% 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

16 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Prognostic value ofWorld journal of gastrointestinal oncology · 2024
    Article
  12. Article
  13. Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023
    Review
  14. Lung Cancer through Transcription Factors.International journal of molecular sciences · 2023
    Article
  15. Review
  16. 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

16 authors at 1 institution in 1 country.

David W ShiaUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
WooSuk ChoiUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Preethi VijayarajUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Valarie VuongUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Jenna M SandlinUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Michelle M LuUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.ORCID 0000-0002-6828-0657
Adam AzizUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Caliope MarinUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Cody J ArosUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Chandani SenUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Abdo DurraUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.ORCID 0000-0002-8738-9674
Andrew J LundUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Arunima PurkayasthaUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Tammy M RickabaughUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
Thomas G GraeberDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, University of California, Los Angeles, CA, 90095, USA.ORCID 0000-0001-8574-9181
Brigitte N GompertsUCLA Children's Discovery and Innovation Institute, Mattel Children's Hospital UCLA, Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. bgomperts@mednet.ucla.edu.ORCID 0000-0002-1809-723X
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) remains a lethal disease with a dismal overall survival rate of 6% despite promising responses to upfront combination chemotherapy. The key drivers of such rapid mortality include early metastatic dissemination in the natural course of the disease and the near guaranteed emergence of chemoresistant disease. Here, we found that we could model the regression and relapse seen in clinical SCLC in vitro. We utilized time-course resolved RNA-sequencing to globally profile transcriptome changes as SCLC cells responded to a combination of cisplatin and etoposide-the standard-of-care in SCLC. Comparisons across time points demonstrated a distinct transient transcriptional state resembling embryonic diapause. Differential gene expression analysis revealed that expression of the PEA3 transcription factors ETV4 and ETV5 were transiently upregulated in the surviving fraction of cells which we determined to be necessary for efficient clonogenic expansion following chemotherapy. The FGFR-PEA3 signaling axis guided the identification of a pan-FGFR inhibitor demonstrating in vitro and in vivo efficacy in delaying progression following combination chemotherapy, observed inhibition of phosphorylation of the FGFR adaptor FRS2 and corresponding downstream MAPK and PI3K-Akt signaling pathways. Taken together, these data nominate PEA3 transcription factors as key mediators of relapse progression in SCLC and identify a clinically actionable small molecule candidate for delaying relapse of SCLC.

Indexed as

Lung NeoplasmsSmall Cell Lung CarcinomaCell Line, TumorHumansNeoplasm Recurrence, LocalPhosphatidylinositol 3-KinasesTranscription FactorsPhosphatidylinositol 3-KinasesTranscription Factors

Identifiers

PMID36509998
PMCPMC9898033
OpenAlexW4311216454

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.