PMID- 36706514
OWN - NLM
STAT- MEDLINE
DCOM- 20230515
LR  - 20230517
IS  - 2468-2942 (Electronic)
IS  - 2468-2942 (Linking)
VI  - 35
DP  - 2023
TI  - Niclosamide in prostate cancer: An inhibitor of AR-V7, a mitochondrial uncoupler, 
      or more?
PG  - 100685
LID - S2468-2942(23)00006-0 [pii]
LID - 10.1016/j.ctarc.2023.100685 [doi]
AB  - A recent phase Ib study investigating the use of reformulated niclosamide in 
      combination with abiraterone and prednisone in patients with castration-resistant 
      prostate cancer (CRPC) demonstrated encouraging preliminary efficacy with low 
      toxicity. Preclinical studies have reported that niclosamide at clinically 
      relevant concentrations inhibits androgen receptor splice variant 7 (AR-V7), a 
      known tumor driver in CRPC. However, the magnitude of anti-tumor effects of 
      niclosamide either used alone or in combination with abiraterone in these 
      experimental models, far exceeded what could have been explained as a simple 
      AR-V7 inhibition. Niclosamide at clinically relevant concentrations also acts as 
      an oxidative phosphorylation (OxPhos) uncoupler in mitochondria. This raises the 
      question whether the observed effects of niclosamide were partly mediated by 
      OxPhos inhibition. Most OxPhos inhibitors did not demonstrate selectivity towards 
      cancer cells and failed to enter clinical practice due to unacceptable toxicity. 
      However, some mitochondrial uncouplers have greater cytotoxicity against 
      cancerous cells compared to non-cancerous. Hyperpolarization of cancer cell 
      mitochondria, or the more alkaline mitochondrial matrix of cancer cells could be 
      potential reasons for this. Niclosamide can also alter Wnt/beta-catenin, mTOR, 
      Notch, NF-kB and STAT3 signaling pathways. Hence, the mechanism of action of 
      reformulated niclosamide in CRPC patients requires further investigation. This 
      will potentially lead to new opportunities to develop and investigate even more 
      selective and effective treatments against prostate cancer.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Sakellakis, Minas
AU  - Sakellakis M
AD  - Hellenic GU Cancer Group, Athens, Greece; Department of Medical Oncology, 
      Metropolitan Hospital, Athens, 18547, Greece. Electronic address: 
      doctorsakellakis@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230122
PL  - England
TA  - Cancer Treat Res Commun
JT  - Cancer treatment and research communications
JID - 101694651
RN  - 0 (Receptors, Androgen)
RN  - 8KK8CQ2K8G (Niclosamide)
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Male
MH  - Humans
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy/pathology
MH  - Receptors, Androgen
MH  - Niclosamide/pharmacology/therapeutic use
MH  - *Antineoplastic Agents/pharmacology/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - AR-V7
OT  - Inhibitor
OT  - Niclosamide
OT  - Prostate cancer
OT  - Uncouplers
COIS- Declaration of Competing Interest The author reports no financial or 
      non-financial conflicts of interest.
EDAT- 2023/01/28 06:00
MHDA- 2023/05/15 06:42
CRDT- 2023/01/27 18:07
PHST- 2022/12/07 00:00 [received]
PHST- 2023/01/11 00:00 [revised]
PHST- 2023/01/13 00:00 [accepted]
PHST- 2023/05/15 06:42 [medline]
PHST- 2023/01/28 06:00 [pubmed]
PHST- 2023/01/27 18:07 [entrez]
AID - S2468-2942(23)00006-0 [pii]
AID - 10.1016/j.ctarc.2023.100685 [doi]
PST - ppublish
SO  - Cancer Treat Res Commun. 2023;35:100685. doi: 10.1016/j.ctarc.2023.100685. Epub 
      2023 Jan 22.