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Published on: December 19, 2019
Skin Carcinogenesis Studies Using Mouse Models with Altered Polyamines
Shannon L Nowotarski1, David J Feith2, Lisa M Shantz3
1Department of Biochemistry, The Pennsylvania State University Berks College, Reading, PA, USA.
Abstract:
Nonmelanoma skin cancer (NMSC) is a major health concern worldwide. With increasing numbers in high-risk groups such as organ transplant recipients and patients taking photosensitizing medications, the incidence of NMSC continues to rise. Mouse models of NMSC allow us to better understand the molecular signaling cascades involved in skin tumor development in order to identify novel therapeutic strategies. Here we review the models designed to determine the role of the polyamines in NMSC development and maintenance. Elevated polyamines are absolutely required for tumor growth, and dysregulation of their biosynthetic and catabolic enzymes has been observed in NMSC. Studies using mice with genetic alterations in epidermal polyamines suggest that they play key roles in tumor promotion and epithelial cell survival pathways, and recent clinical trials indicate that pharmacological inhibitors of polyamine metabolism show promise in individuals at high risk for NMSC.
Insights
Nonmelanoma skin cancer (NMSC) incidence is rising. Polyamines are essential for tumor growth, and targeting their metabolism shows promise for NMSC treatment in high-risk individuals.
Area of Science:
- Dermatology and Oncology
- Molecular Biology
- Cancer Research
Background:
- Nonmelanoma skin cancer (NMSC) is a significant global health issue, with increasing incidence in immunosuppressed individuals and those on photosensitizing drugs.
- Understanding the molecular mechanisms driving NMSC is crucial for developing effective therapeutic strategies.
- Polyamines, essential for cell growth, are implicated in NMSC development and maintenance.
Purpose of the Study:
- To review mouse models used to investigate the role of polyamines in NMSC.
- To summarize findings on polyamine metabolism in NMSC development.
- To highlight the therapeutic potential of targeting polyamine pathways.
Main Methods:
- Review of existing literature on NMSC mouse models.
- Analysis of studies investigating polyamine metabolism in skin cancer.
- Examination of data from clinical trials on polyamine inhibitors.
Main Results:
- Elevated polyamines are critical for NMSC tumor growth.
- Dysregulation of polyamine biosynthetic and catabolic enzymes is observed in NMSC.
- Genetic alterations in epidermal polyamines in mice highlight their role in tumor promotion and cell survival.
Conclusions:
- Polyamines play a key role in NMSC development and progression.
- Pharmacological inhibition of polyamine metabolism is a promising therapeutic strategy for NMSC, particularly in high-risk populations.
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