Evidence map›Paper›PMID 31387608›Full record

ArticleJournal of experimental & clinical cancer research : CR2019

The small molecule WNT/β-catenin inhibitor CWP232291 blocks the growth of castration-resistant prostate cancer by activating the endoplasmic reticulum stress pathway.

Sahyun Pak, Sejun Park, Yunlim Kim, Jung-Hyuck Park, Chan-Hee Park, Kyoung-June Lee, Choung-Soo Kim, Hanjong Ahn

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
5.0field-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

40 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.

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  10. Why Is Wnt/β-Catenin Not Yet Targeted in Routine Cancer Care?Pharmaceuticals (Basel, Switzerland) · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Sahyun PakDepartment of Urology, Center for Urologic Cancer, National Cancer Center, Goyang, South Korea.
Sejun ParkDepartment of Urology, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, South Korea.
Yunlim KimDepartment of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Jung-Hyuck ParkDrug Discovery Center, JW Pharmaceutical Corporation, Seoul, South Korea.
Chan-Hee ParkDrug Discovery Center, JW Pharmaceutical Corporation, Seoul, South Korea.
Kyoung-June LeeJW Creagene Corporation, Seongnam, South Korea.
Choung-Soo KimDepartment of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Hanjong AhnDepartment of Urology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. hjahn@amc.seoul.kr.
JW Pharmaceutical (South Korea) · KRAsan Medical Center · KRNational Cancer Center · KRUlsan College · KRUniversity of Ulsan · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAndrogen receptor (AR)-targeted treatments improve the survival of castration-resistant prostate cancer (CRPC) patients; however, secondary resistance to these agents ultimately occurs in virtually all patients. Therefore, alternative therapeutic targets are urgently needed. Since growing evidence demonstrates that WNT/β-catenin signaling plays an important role in CRPC, the antitumor activity and mechanism of action of CWP232291, a small molecule β-catenin inhibitor, were investigated in prostate cancer.

methodsWe assessed the antitumor activity of CWP232291 in prostate cancer cell lines and primary cells derived from CRPC patients. The effect of CWP232291 on apoptotic cell death, endoplasmic reticulum (ER) stress, cell viability, and WNT/β-catenin signaling was evaluated by flow cytometry, western blotting, luciferase reporter assay, and fluorescence microscopy. Antitumor efficacy was assessed in two CRPC xenograft mouse models.

resultsCWP232291 induced ER stress, resulting in upregulation of the proapoptotic protein CHOP and activation of caspase-3-dependent apoptosis. In addition, CWP232291 suppressed the expression of β-catenin by affecting WNT-dependent transcriptional activity, and downregulated AR and its splice variants in prostate cancer cells. Antitumor activity was observed in prostate cancer cells in vitro and ex vivo, and antitumor efficacy was observed in vivo.

conclusionsBeyond providing preclinical evidence of therapeutic efficacy for the novel small molecule β-catenin inhibitor CWP232291 in CRPC, our results show that inducing ER stress and targeting WNT/β-catenin signaling may be a novel strategy against CRPC.

Indexed as

Castration-resistantEndoplasmic reticulum stressProstate cancerWNT signaling pathway

Identifiers

PMID31387608
PMCPMC6685284
OpenAlexW2966213177

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.