Evidence map›Paper›PMID 32139878›Full record

SynthesisProstate cancer and prostatic diseases2020

Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.

Changxue Lu, Landon C Brown, Emmanuel S Antonarakis, Andrew J Armstrong, Jun Luo

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

Synthesis in Prostate cancer and prostatic diseases, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

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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

5 authors at 2 institutions in 1 country.

Changxue LuDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Landon C BrownDepartments of Medicine, Surgery, and Pharmacology and Cancer Biology, Divisions of Medical Oncology and Urology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0002-5231-4859
Emmanuel S Antonarakis *Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Andrew J Armstrong *Departments of Medicine, Surgery, and Pharmacology and Cancer Biology, Divisions of Medical Oncology and Urology, Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, Durham, NC, USA.ORCID http://orcid.org/0000-0001-7012-1754
Jun Luo *Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jluo1@jhmi.edu.
Johns Hopkins University · USDuke University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Targeting convergent oncogenic signaling during AR inhibition to overcome metastasis and immune evasion in prostate cancerR01CA233585 · NCI · DUKE UNIVERSITY · PI ARMSTRONG, ANDREW J · 2019 to 2023
$2.2M
The aberrant androgen receptor underlies abiraterone/enzalutamide resistanceR01CA185297 · NCI · JOHNS HOPKINS UNIVERSITY · PI ANTONARAKIS, EMMANUEL S., LUO, JUN · 2015 to 2018
$1.5M
NCI NIH HHS P30 CA006973NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA185297NCI NIH HHS R01 CA233585
6 · The paper itself

Abstract

backgroundThe androgen receptor (AR) is a key prostate cancer drug target. Suppression of AR signaling mediated by the full-length AR (AR-FL) is the therapeutic goal of all existing AR-directed therapies. AR-targeting agents impart therapeutic benefit, but lead to AR aberrations that underlie disease progression and therapeutic resistance. Among the AR aberrations specific to castration-resistant prostate cancer (CRPC), AR variants (AR-Vs) have emerged as important indicators of disease progression and therapeutic resistance.

methodsWe conducted a systemic review of the literature focusing on recent laboratory studies on AR-Vs following our last review article published in 2016. Topics ranged from measurement and detection, molecular origin, regulation, genomic function, and preclinical therapeutic targeting of AR-Vs. We provide expert opinions and perspectives on these topics.

resultsTranscript sequences for 22 AR-Vs have been reported in the literature. Different AR-Vs may arise through different mechanisms, and can be regulated by splicing factors and dictated by genomic rearrangements, but a low-androgen environment is a prerequisite for generation of AR-Vs. The unique transcript structures allowed development of in situ and in-solution measurement and detection methods, including mRNA and protein detection, in both tissue and blood specimens. AR-V7 remains the main measurement target and the most extensively characterized AR-V. Although AR-V7 coexists with AR-FL, genomic functions mediated by AR-V7 do not require the presence of AR-FL. The distinct cistromes and transcriptional programs directed by AR-V7 and their coregulators are consistent with genomic features of progressive disease in a low-androgen environment. Preclinical development of AR-V-directed agents currently focuses on suppression of mRNA expression and protein degradation as well as targeting of the amino-terminal domain.

conclusionsCurrent literature continues to support AR-Vs as biomarkers and therapeutic targets in prostate cancer. Laboratory investigations reveal both challenges and opportunities in targeting AR-Vs to overcome resistance to current AR-directed therapies.

Indexed as

Alternative SplicingAndrogen Receptor AntagonistsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorClinical Decision-MakingDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticGenetic TestingHumansMalePrecision MedicineProgression-Free SurvivalProstatic Neoplasms, Castration-ResistantProtein IsoformsProteolysisReceptors, AndrogenAndrogen Receptor AntagonistsAR protein, humanBiomarkers, TumorProtein IsoformsReceptors, Androgen

Identifiers

PMID32139878
PMCPMC7725416
OpenAlexW3009540553

What OpenQuestion holds

Textmetadata
LicenceTDM
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.