PMID- 34997154
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20231114
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jan 7
TI  - The rexinoid V-125 reduces tumor growth in preclinical models of breast and lung 
      cancer.
PG  - 293
LID - 10.1038/s41598-021-04415-0 [doi]
LID - 293
AB  - Rexinoids are ligands which activate retinoid X receptors (RXRs), regulating 
      transcription of genes involved in cancer-relevant processes. Rexinoids have 
      anti-neoplastic activity in multiple preclinical studies. Bexarotene, used to 
      treat cutaneous T cell lymphoma, is the only FDA-approved rexinoid. Bexarotene 
      has also been evaluated in clinical trials for lung and metastatic breast cancer, 
      wherein subsets of patients responded despite advanced disease. By modifying 
      structures of known rexinoids, we can improve potency and toxicity. We previously 
      screened a series of novel rexinoids and selected V-125 as the lead based on 
      performance in optimized in vitro assays. To validate our screening paradigm, we 
      tested V-125 in clinically relevant mouse models of breast and lung cancer. V-125 
      significantly (p < 0.001) increased time to tumor development in the MMTV-Neu 
      breast cancer model. Treatment of established mammary tumors with V-125 
      significantly (p < 0.05) increased overall survival. In the A/J lung cancer 
      model, V-125 significantly (p < 0.01) decreased number, size, and burden of lung 
      tumors. Although bexarotene elevated triglycerides and cholesterol in these 
      models, V-125 demonstrated an improved safety profile. These studies provide 
      evidence that our screening paradigm predicts novel rexinoid efficacy and suggest 
      that V-125 could be developed into a new cancer therapeutic.
CI  - (c) 2022. The Author(s).
FAU - Reich, Lyndsey A
AU  - Reich LA
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA.
FAU - Moerland, Jessica A
AU  - Moerland JA
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA.
FAU - Leal, Ana S
AU  - Leal AS
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA.
FAU - Zhang, Di
AU  - Zhang D
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA.
FAU - Carapellucci, Sarah
AU  - Carapellucci S
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA.
FAU - Lockwood, Beth
AU  - Lockwood B
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA.
FAU - Jurutka, Peter W
AU  - Jurutka PW
AD  - School of Mathematical and Natural Sciences, New College of Interdisciplinary 
      Arts and Sciences, Arizona State University, Glendale, AZ, USA.
FAU - Marshall, Pamela A
AU  - Marshall PA
AD  - School of Mathematical and Natural Sciences, New College of Interdisciplinary 
      Arts and Sciences, Arizona State University, Glendale, AZ, USA.
FAU - Wagner, Carl E
AU  - Wagner CE
AD  - School of Mathematical and Natural Sciences, New College of Interdisciplinary 
      Arts and Sciences, Arizona State University, Glendale, AZ, USA.
FAU - Liby, Karen T
AU  - Liby KT
AD  - Department of Pharmacology and Toxicology, Michigan State University College of 
      Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East 
      Lansing, MI, 48824, USA. libykare@msu.edu.
LA  - eng
GR  - R15 CA249617/CA/NCI NIH HHS/United States
GR  - T32 GM142521/GM/NIGMS NIH HHS/United States
GR  - 1R15CA139364-01A2/NH/NIH HHS/United States
GR  - R15 CA139364/CA/NCI NIH HHS/United States
GR  - 1R15CA249617-01/NH/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220107
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Breast Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Lung Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - Mice, Transgenic
MH  - Retinoid X Receptors/*agonists/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - Tumor Burden/drug effects
PMC - PMC8742020
COIS- Patent applications covering the novel materials described in this work have been 
      applied for on behalf of the Arizona Board of Regents; Peter W. Jurutka, Pamela 
      A. Marshall, and Carl E. Wagner are named inventors. Lyndsey A. Reich, Jessica A. 
      Moerland, Ana S. Leal, Di Zhang, Sarah Carapellucci, Beth Lockwood, and Karen T. 
      Liby declare no competing interests.
EDAT- 2022/01/09 06:00
MHDA- 2022/02/25 06:00
PMCR- 2022/01/07
CRDT- 2022/01/08 06:01
PHST- 2021/08/18 00:00 [received]
PHST- 2021/12/20 00:00 [accepted]
PHST- 2022/01/08 06:01 [entrez]
PHST- 2022/01/09 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2022/01/07 00:00 [pmc-release]
AID - 10.1038/s41598-021-04415-0 [pii]
AID - 4415 [pii]
AID - 10.1038/s41598-021-04415-0 [doi]
PST - epublish
SO  - Sci Rep. 2022 Jan 7;12(1):293. doi: 10.1038/s41598-021-04415-0.