Evidence map›Paper›PMID 28383660›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2017

CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair.

T R Shenoy, G Boysen, M Y Wang, Q Z Xu, W Guo, F M Koh, C Wang, L Z Zhang, Y Wang, V Gil and 16 more

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

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

79 citing papers in PubMed, 121 citations in OpenAlex.

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  12. Organoids technology in cancer research: from basic applications to advancedFrontiers in cell and developmental biology · 2025
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 6 institutions in 3 countries.

T R ShenoyDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, USA.
G BoysenThe Institute of Cancer Research, London, UK.
M Y WangThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Q Z XuThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
W GuoThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
F M KohEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research and Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, USA.
C WangDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, USA.
L Z ZhangThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Y WangDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, USA.
V GilThe Institute of Cancer Research, London, UK.
S AzizThe Institute of Cancer Research, London, UK.
R ChristovaThe Institute of Cancer Research, London, UK.
D N RodriguesThe Institute of Cancer Research, London, UK.
M CrespoThe Institute of Cancer Research, London, UK.
P RescignoProstate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London, UK.
N TunariuProstate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London, UK.
R RiisnaesThe Institute of Cancer Research, London, UK.
Z ZafeiriouProstate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, London, UK.
P FlohrThe Institute of Cancer Research, London, UK.
W YuanThe Institute of Cancer Research, London, UK.
E KnightThe Institute of Cancer Research, London, UK.
A SwainThe Institute of Cancer Research, London, UK.
M Ramalho-SantosEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research and Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, USA.
D Y XuThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
J de BonoThe Institute of Cancer Research, London, UK.
H WuDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, USA.
Institute of Cancer Research · GBCenter for Life Sciences · CNUniversity of California, Los Angeles · USRoyal Marsden NHS Foundation Trust · GBBroad Center · USUniversity of California, San Francisco · US

Funding

UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6M
Influences of the Microenvironment on Cancer Stem CellsU01CA164188 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NELSON, PETER S, WITTE, OWEN N. · 2011 to 2015
$2.9M
Role of Chd1 in the transcriptional output and development of pluripotent cellsR01GM113014 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RAMALHO-SANTOS, MIGUEL · 2015 to 2018
$1.2M
NCI NIH HHS P50 CA092131NCI NIH HHS U01 CA164188NIGMS NIH HHS R01 GM113014
6 · The paper itself

Abstract

backgroundDeletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized by SPOP mutation and higher genomic instability. However, the role of CHD1 in PCa development in vivo and its clinical utility remain unclear. PATIENTS AND

methodsTo study the role of CHD1 in PCa development and its loss in clinical management, we generated a genetically engineered mouse model with prostate-specific deletion of murine Chd1 as well as isogenic CHD1 wild-type and homozygous deleted human benign and PCa lines. We also developed patient-derived organoid cultures and screened patients with metastatic PCa for CHD1 loss.

resultsWe demonstrate that CHD1 loss sensitizes cells to DNA damage and causes a synthetic lethal response to DNA damaging therapy in vitro, in vivo, ex vivo, in patient-derived organoid cultures and in a patient with metastatic PCa. Mechanistically, CHD1 regulates 53BP1 stability and CHD1 loss leads to decreased error-free homologous recombination (HR) repair, which is compensated by increased error-prone non-homologous end joining (NHEJ) repair for DNA double-strand break (DSB) repair.

conclusionsOur study provides the first in vivo and in patient evidence supporting the role of CHD1 in DSB repair and in response to DNA damaging therapy. We uncover mechanistic insights that CHD1 modulates the choice between HR and NHEJ DSB repair and suggest that CHD1 loss may contribute to the genomic instability seen in this subset of PCas.

Indexed as

DNA Breaks, Double-StrandedAnimalsCdh1 ProteinsCell Line, TumorCross-Linking ReagentsDNA End-Joining RepairDose-Response Relationship, DrugDown-RegulationGene DeletionGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseHumansMaleMice, KnockoutPhenotypePoly(ADP-ribose) Polymerase InhibitorsCdh1 ProteinsCross-Linking ReagentsFZR1 protein, humanFzr1 protein, mousePoly(ADP-ribose) Polymerase InhibitorsTP53BP1 protein, humanTrp53bp1 protein, mouseTumor Suppressor p53-Binding Protein 1chromatin remodeler CHD1DDRhomologous recombinationnon-homologous end joiningPCasynthetic lethality

Identifiers

PMID28383660
PMCPMC5834074
OpenAlexW2607198330

What OpenQuestion holds

Textmetadata
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.