Evidence map›Paper›PMID 27349498›Full record

ArticleProstate cancer and prostatic diseases2016

Reversible lysine-specific demethylase 1 antagonist HCI-2509 inhibits growth and decreases c-MYC in castration- and docetaxel-resistant prostate cancer cells.

S Gupta, A Weston, J Bearrs, T Thode, A Neiss, R Soldi, S Sharma

Open access · hybridAbstract read
In one paragraph

Article in Prostate cancer and prostatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.3field-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

25 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
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  6. Review
  7. Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023
    Review
  8. Article
  9. Article
  10. Review
  11. Gene Transactivation and Transrepression in MYC-Driven Cancers.International journal of molecular sciences · 2021
    Review
  12. Review
  13. Review
  14. Targeting the Immune system and Epigenetic Landscape of Urological Tumors.International journal of molecular sciences · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Pharmacological Inhibition of LSD1 for Cancer Treatment.Molecules (Basel, Switzerland) · 2018
    Review
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

7 authors at 3 institutions in 1 country.

S GuptaGU Medical Oncology, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
A WestonGU Medical Oncology, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
J BearrsGU Medical Oncology, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
T ThodeGU Medical Oncology, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
A NeissGU Medical Oncology, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
R SoldiBeta Cat Pharmaceuticals, Houston, TX, USA.
S SharmaGU Medical Oncology, Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Huntsman Cancer Institute · USUniversity of Utah · USBetaCat Pharmaceuticals (United States) · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
NCI NIH HHS P30 CA042014
6 · The paper itself

Abstract

backgroundLysine-specific demethylase 1 (LSD1 or KDM1A) overexpression correlates with poor survival and castration resistance in prostate cancer. LSD1 is a coregulator of ligand-independent androgen receptor signaling promoting c-MYC expression. We examined the antitumor efficacy of LSD1 inhibition with HCI-2509 in advanced stages of prostate cancer.

methodsCell survival, colony formation, histone methylation, c-MYC level, c-MYC expression, cell cycle changes and in vivo efficacy were studied in castration-resistant prostate cancer cells upon treatment with HCI-2509. In vitro combination studies, using HCI-2509 and docetaxel, were performed to assess the synergy. Cell survival, colony formation, histone methylation and c-myc levels were studied in docetaxel-resistant prostate cancer cells treated with HCI-2509.

resultsHCI-2509 is cytotoxic and inhibits colony formation in castration-resistant prostate cancer cells. HCI-2509 treatment causes a dose-dependent increase in H3K9me2 (histone H3lysine 9) levels, a decrease in c-MYC protein, inhibition of c-MYC expression and accumulation in the G0/G1 phase of the cell cycle in these cells. PC3 xenografts in mice have a significant reduction in tumor burden upon treatment with HCI-2509 with no associated myelotoxicity or weight loss. More synergy is noted at sub-IC

conclusionsLSD1 inhibition with HCI-2509 decreases the c-MYC level in poorly differentiated prostate cancer cell lines and has a therapeutic potential in castration- and docetaxel-resistant prostate cancer.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationCell SurvivalDocetaxelDrug Resistance, NeoplasmFemaleG1 PhaseHistone DemethylasesHistonesHumansLigandsMaleMiceMice, NudeAntineoplastic AgentsDocetaxelHistone DemethylasesHistonesKDM1A protein, humanLigandsProto-Oncogene Proteins c-mycReceptors, AndrogenTaxoids

Identifiers

PMID27349498
PMCPMC5133270
OpenAlexW2460507268

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.