An In Vivo Study of LNS8801, a GPER Agonist, in a Spontaneous Melanoma-Prone Mouse Model, TGS
Christina Marinaro1,2, John Sauer1,3, Christopher A Natale4,5
1Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers University, The State University of New Jersey, New Brunswick, New Jersey, USA.
Abstract:
Melanoma is the most aggressive and deadly form of skin cancer that arises from the transformation of melanocytes, the pigment producing cells of the skin. In the year 2024 there will be approximately 10,000 new cases of melanoma diagnosed and approximately 8,000 deaths attributed to melanoma in the United States. In this study we treated a group of male and female transgenic mice that spontaneously develop metastatic melanoma, TGS, with a G-protein-coupled estrogen receptor agonist LNS8801 to assess the efficacy on disease progression. A second group of male and female TGS mice was also exposed to UVB irradiation to mimic exposure to sunlight. Over the course of the 32-week experiment, visible images were taken by the small animal imaging IVIS system to track tumor progression, and blood and tissue samples were collected for molecular analyses. Results showed that sex-biased effects were observed in the efficacy of LNS8801 and that LNS8801 shows a UV-protective influence in both male and female TGS mice.
Insights
This study investigated LNS8801, a G-protein-coupled estrogen receptor agonist, for melanoma treatment in mice. LNS8801 demonstrated sex-biased efficacy and provided UV protection against melanoma progression.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Melanoma is an aggressive skin cancer originating from melanocytes.
- UVB exposure is a known risk factor for melanoma development.
- Transgenic mice (TGS) spontaneously develop metastatic melanoma, serving as a model.
Purpose of the Study:
- To evaluate the efficacy of LNS8801, a G-protein-coupled estrogen receptor agonist, in treating metastatic melanoma.
- To assess the impact of UVB irradiation on melanoma progression in TGS mice.
- To investigate potential sex-biased effects of LNS8801 treatment and its UV-protective influence.
Main Methods:
- Treatment of male and female TGS mice with LNS8801.
- Exposure of a separate group of TGS mice to UVB irradiation.
- Monitoring tumor progression using the IVIS imaging system over 32 weeks.
- Collection of blood and tissue samples for molecular analysis.
Main Results:
- Sex-biased effects were observed in the efficacy of LNS8801 treatment.
- LNS8801 demonstrated a UV-protective influence in both male and female TGS mice.
- Tumor progression was monitored and molecular analyses were performed.
Conclusions:
- LNS8801 exhibits potential as a therapeutic agent for melanoma, with efficacy influenced by sex.
- LNS8801 offers a protective effect against UV-induced melanoma progression.
- Further research is warranted to explore the mechanisms behind these findings.
