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1Division of Dermatopharmacology, Department of Dermatology, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903, USA. John_DiGiovanni_MD@Brown.edu
Abstract:
Patients who develop large numbers of skin cancers suffer increased morbidity and mortality. A high skin cancer risk can result from inherited disorders such as xeroderma pigmentosum (abnormal repair of UV-induced DNA damage) or the nevoid basal cell carcinoma syndrome (tumor suppressor gene abnormality). The efficacy of systemic retinoid skin cancer chemoprevention was first demonstrated in these disorders. Since the mechanism of cancer prevention was not thought to involve correction of the underlying defect causing the disorder, individuals at high risk for new skin cancers from other causes may also benefit from this approach. With the success of organ transplantation, there is a growing population of transplant recipients living long, active lives who also have sustained chronic UV damage. This population is at high risk for developing aggressive squamous cell carcinomas. In this population, extensive skin involvement with human papilloma virus induced warts and actinic keratoses results in difficulty with diagnosis and monitoring for these dangerous malignancies. Patients who have received treatment with agents that cause DNA damage, such as X-radiation, may also have a high skin cancer risk. Retinoid chemoprevention may also be of benefit in the management of selected patients with these iatrogenic conditions. This evolving therapeutic role has heightened the need for the development of new retinoids, with more efficacy and less toxicity, for cancer chemoprevention.
Insights
Systemic retinoids can prevent skin cancers in high-risk individuals, including transplant recipients and those with inherited DNA repair disorders. Further research into novel retinoids is needed for improved efficacy and reduced toxicity in cancer chemoprevention.
Area of Science:
- Dermatology
- Oncology
- Pharmacology
Background:
- High skin cancer incidence and mortality are significant concerns, particularly in individuals with inherited DNA repair defects (e.g., xeroderma pigmentosum) or compromised immune systems (e.g., organ transplant recipients).
- Chronic UV damage and iatrogenic causes (e.g., X-radiation) also contribute to elevated skin cancer risk.
- Existing chemoprevention strategies using systemic retinoids have shown efficacy in specific high-risk populations.
Purpose of the Study:
- To explore the potential benefits of systemic retinoid chemoprevention for a broader range of individuals at high risk for skin cancer.
- To investigate the utility of retinoids in managing skin conditions in organ transplant recipients and patients with iatrogenic risk factors.
- To highlight the need for developing more effective and less toxic retinoid agents for cancer chemoprevention.
Main Methods:
- Review of existing literature on retinoid chemoprevention efficacy in inherited skin cancer syndromes.
- Analysis of the risk factors and clinical challenges associated with skin cancer development in organ transplant recipients.
- Consideration of retinoid therapy for patients with iatrogenic skin cancer risk.
- Discussion on the potential for novel retinoid development.
Main Results:
- Systemic retinoids have demonstrated efficacy in preventing skin cancers in patients with inherited DNA repair disorders.
- Organ transplant recipients with chronic UV damage and immunosuppression face a high risk of aggressive squamous cell carcinomas.
- Retinoid chemoprevention may offer benefits for selected patients with iatrogenic skin cancer risk factors.
Conclusions:
- The chemopreventive potential of systemic retinoids extends beyond inherited disorders to other high-risk populations.
- Effective management of skin conditions like warts and actinic keratoses in transplant recipients is crucial for monitoring malignancies.
- Development of next-generation retinoids with enhanced efficacy and reduced toxicity is essential for advancing skin cancer chemoprevention.
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