Evidence map›Paper›PMID 30287662›Full record

ArticleScience (New York, N.Y.)2018

Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage.

Jung Wook Park, John K Lee, Katherine M Sheu, Liang Wang, Nikolas G Balanis, Kim Nguyen, Bryan A Smith, Chen Cheng, Brandon L Tsai, Donghui Cheng and 4 more

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

Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
212citing papers in PubMed, 2 pooled it
14.3field-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

212 citing papers in PubMed, 2 syntheses or guidelines pooled it, 357 citations in OpenAlex.

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  13. Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  20. RUNX1T1 drives stem-like small-cell neuroendocrine prostate cancer identity.Frontiers in cell and developmental biology · 2026
    Article

152 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Jung Wook ParkDepartment of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-4798-9621
John K LeeDivision of Hematology and Oncology, Department of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Katherine M SheuDepartment of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0002-3811-3356
Liang WangDepartment of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Nikolas G BalanisDepartment of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Kim NguyenDepartment of Ecology and Evolutionary Biology, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Bryan A SmithDepartment of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Chen ChengDepartment of Biological Chemistry, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Brandon L TsaiDepartment of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Donghui ChengDepartment of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Jiaoti HuangDepartment of Pathology, School of Medicine, Duke University, Durham, NC 27710, USA.ORCID 0000-0003-1195-1998
Siavash K KurdistaniDepartment of Biological Chemistry, University of California-Los Angeles, Los Angeles, CA 90095, USA.ORCID 0000-0003-3295-3511
Thomas G GraeberDepartment of Molecular and Medical Pharmacology, University of California-Los Angeles, Los Angeles, CA 90095, USA. owenwitte@mednet.ucla.edu tgraeber@mednet.ucla.edu.ORCID 0000-0001-8574-9181
Owen N WitteDepartment of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA. owenwitte@mednet.ucla.edu tgraeber@mednet.ucla.edu.
University of California, Los Angeles · USDuke University · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6M
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
The Effect of Nanoparticle Encapsulated Resveratrol on Treatment of PeriodontitisKL2TR001882 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Elizabeta Nemeth · 2016 to 2026
$13.1M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LO, ROGER S · 2013 to 2017
$8.4M
Targeting Genomic Instability in Lethal Neuroendocrine Prostate CancerR01CA222877 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GRAEBER, THOMAS G, WITTE, OWEN N. · 2018 to 2022
$2.6M
A novel strategy to identify prostate cancer biomarkers for patient managementR01CA172603 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HUANG, JIAOTI · 2013 to 2017
$1.6M
Dynamics of Histone Acetylation in Cancer Cell PhysiologyR01CA178415 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KURDISTANI, SIAVASH · 2013 to 2017
$1.6M
Histologic and Immunohistochemical Biomarkers for Heavily Treated Metastatic Prostate Cancer.R01CA205001 · NCI · DUKE UNIVERSITY · PI HUANG, JIAOTI · 2016 to 2020
$1.3M
Defining the Essential Determinants of Prostate Cancer Differentiation StatesR00CA218731 · NCI · DUKE UNIVERSITY · PI PARK, JUNG WOOK · 2019 to 2021
$747k
Defining the Essential Determinants of Prostate Cancer Differentiation StatesK99CA218731 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PARK, JUNG WOOK · 2017 to 2018
$258k
NCATS NIH HHS KL2 TR001882NCI NIH HHS K99 CA218731NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA092131NCI NIH HHS R00 CA218731NCI NIH HHS R01 CA172603NCI NIH HHS R01 CA178415NCI NIH HHS R01 CA205001NCI NIH HHS R01 CA222877NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs.

Indexed as

CarcinogenesisCarcinoma, NeuroendocrineCell LineageCell Line, TumorCellular ReprogrammingCellular Reprogramming TechniquesDrug Delivery SystemsEpithelial CellsEpitheliumHumansLungLung NeoplasmsMaleProstateProstatic NeoplasmsRetinoblastoma ProteinRetinoblastoma ProteinTumor Suppressor Protein p53

Identifiers

PMID30287662
PMCPMC6414229
OpenAlexW2895496651

What OpenQuestion holds

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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.