PMID- 34638488
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231107
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 19
DP  - 2021 Oct 6
TI  - The RXR Agonist MSU42011 Is Effective for the Treatment of Preclinical HER2+ 
      Breast Cancer and Kras-Driven Lung Cancer.
LID - 10.3390/cancers13195004 [doi]
LID - 5004
AB  - (1) Background: Notwithstanding numerous therapeutic advances, 176,000 deaths 
      from breast and lung cancers will occur in the United States in 2021 alone. The 
      tumor microenvironment and its modulation by drugs have gained increasing 
      attention and relevance, especially with the introduction of immunotherapy as a 
      standard of care in clinical practice. Retinoid X receptors (RXRs) are members of 
      the nuclear receptor superfamily and upon ligand binding, function as 
      transcription factors to modulate multiple cell functions. Bexarotene, the only 
      FDA-approved RXR agonist, is still used to treat cutaneous T-cell lymphoma. (2) 
      Methods: To test the immunomodulatory and anti-tumor effects of MSU42011, a new 
      RXR agonist, we used two different immunocompetent murine models (MMTV-Neu mice, 
      a HER2 positive model of breast cancer and the A/J mouse model, in which vinyl 
      carbamate is used to initiate lung tumorigenesis) and an immunodeficient 
      xenograft lung cancer model. (3) Results: Treatment of established tumors in 
      immunocompetent models of HER2-positive breast cancer and Kras-driven lung cancer 
      with MSU42011 significantly decreased the tumor burden and increased the ratio of 
      CD8/CD4, CD25 T cells, which correlates with enhanced anti-tumor efficacy. 
      Moreover, the combination of MSU42011 and immunotherapy (anti-PDL1 and anti-PD1 
      antibodies) significantly (p < 0.05) reduced tumor size vs. individual 
      treatments. However, MSU42011 was ineffective in an athymic human A549 lung 
      cancer xenograft model, supporting an immunomodulatory mechanism of action. (4) 
      Conclusions: Collectively, these data suggest that the RXR agonist MSU42011 can 
      be used to modulate the tumor microenvironment in breast and lung cancer.
FAU - Leal, Ana S
AU  - Leal AS
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
FAU - Moerland, Jessica A
AU  - Moerland JA
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
FAU - Zhang, Di
AU  - Zhang D
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
FAU - Carapellucci, Sarah
AU  - Carapellucci S
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
FAU - Lockwood, Beth
AU  - Lockwood B
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
FAU - Krieger-Burke, Teresa
AU  - Krieger-Burke T
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - In Vivo Facility, Michigan State University, East Lansing, MI 48824, USA.
FAU - Aleiwi, Bilal
AU  - Aleiwi B
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - Medicinal Chemistry Facility, Michigan State University, East Lansing, MI 48824, 
      USA.
FAU - Ellsworth, Edmund
AU  - Ellsworth E
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
AD  - Medicinal Chemistry Facility, Michigan State University, East Lansing, MI 48824, 
      USA.
FAU - Liby, Karen T
AU  - Liby KT
AD  - Department of Pharmacology and Toxicology, Michigan State University, East 
      Lansing, MI 48824, USA.
LA  - eng
GR  - Breast Cancer Research Foundation/Breast Cancer Research Foundation/
GR  - Mi-Kickstart/MSU Molecular Discovery Group Pilot Grant/
GR  - Mi-Trac Award/Michigan Economic Development Corporation/
PT  - Journal Article
DEP - 20211006
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8508021
OTO - NOTNLM
OT  - RXR agonist
OT  - breast cancer
OT  - immunotherapy
OT  - lung cancer
OT  - tumor microenvironment
COIS- A.S.L., B.A., E.E., and K.T.L. are named inventors on a patent filed on novel 
      rexinoids and owned by MSU. The other authors have no potential conflict of 
      interest.
EDAT- 2021/10/14 06:00
MHDA- 2021/10/14 06:01
PMCR- 2021/10/06
CRDT- 2021/10/13 01:02
PHST- 2021/07/29 00:00 [received]
PHST- 2021/10/02 00:00 [revised]
PHST- 2021/10/02 00:00 [accepted]
PHST- 2021/10/13 01:02 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/14 06:01 [medline]
PHST- 2021/10/06 00:00 [pmc-release]
AID - cancers13195004 [pii]
AID - cancers-13-05004 [pii]
AID - 10.3390/cancers13195004 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Oct 6;13(19):5004. doi: 10.3390/cancers13195004.