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Oral retinoids and rexinoids in cutaneous T-cell lymphomas
Małgorzata Sokołowska-Wojdyło1, Hanna Lugowska-Umer, Agata Maciejewska-Radomska
1Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland. Head: Prof. Roman Nowicki MD, PhD.
Abstract:
Retinoids are biologically active derivatives of vitamin A modulating cell proliferation, differentiation, apoptosis and altering the immune response. They have been used for years in therapy of cutaneous T-cell lymphomas (CTCL) but the exact mechanism of retinoids' action is unclear. It is based on the presence of specific receptors' families, mediating the biological effects of retinoids on the tumor cells: retinoic acid receptor (RAR) and retinoic X receptor (RXR). Orally administrated bexarotene, the first synthetic selective RXR retinoid, was revealed to be active against the cutaneous manifestation of CTCL. The toxicity profile caused by bexarotene seems to be more limited to laboratory values and better tolerated than classical retinoids, but generally associated with more severe grades of toxicity. Both selective retinoic acid receptor- and retinoic X receptor-mediated retinoids have modest objective response rates and, therefore, most likely will have limited impact as monotherapeutic agents. However, the immunomodulatory effects of RAR and RXR retinoids provide a rational basis for using retinoids in combination with other biologic immune response modifiers, phototherapy and radiotherapy. The authors reviewed the literature on the results of the use of retinoids and rexinoids in patients with mycosis fungoides and Sézary syndrome.
Insights
Retinoids, vitamin A derivatives, modulate cell behavior and immune responses. While effective for cutaneous T-cell lymphomas (CTCL), combination therapies are recommended due to modest monotherapy response rates.
Area of Science:
- Dermatology
- Oncology
- Pharmacology
Background:
- Retinoids, vitamin A derivatives, influence cell proliferation, differentiation, and apoptosis.
- Their mechanism in cutaneous T-cell lymphomas (CTCL) involves retinoic acid receptors (RAR) and retinoic X receptors (RXR).
- Bexarotene, a selective RXR agonist, shows activity against CTCL cutaneous manifestations.
Purpose of the Study:
- To review the literature on retinoid and rexinoid use in mycosis fungoides and Sézary syndrome.
- To understand the mechanisms of retinoid action in CTCL.
- To evaluate the efficacy and toxicity of retinoids in CTCL treatment.
Main Methods:
- Literature review of studies on retinoids and rexinoids in CTCL.
- Analysis of clinical trial data and case reports.
- Examination of the roles of RAR and RXR pathways.
Main Results:
- Both RAR- and RXR-selective retinoids demonstrate modest objective response rates as monotherapy.
- Bexarotene exhibits a distinct toxicity profile, potentially more severe than classical retinoids.
- Retinoids possess immunomodulatory effects beneficial for combination therapies.
Conclusions:
- Retinoids and rexinoids have a role in CTCL management, particularly mycosis fungoides and Sézary syndrome.
- Their limited monotherapy efficacy suggests combination strategies are optimal.
- The immunomodulatory properties support combining retinoids with biologics, phototherapy, or radiotherapy.
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