Retinoic Acid-Related Orphan Receptor (ROR) Inverse Agonists: Potential Therapeutic Strategies for Multiple Inflammatory Diseases?

Jetten, Anton M.; Beak, Ju Youn; Słomiński, Andrzej; Jensen, Brian C.

doi:10.1007/978-3-030-78315-0_14

Cited by 2 publications

(3 citation statements)

References 174 publications

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“…Furthermore, other investigators using animal models of melanoma have shown that IL-17A-deficient mice are susceptible to spontaneous melanoma development [ 647 ]. However, the regulation and role of IL-17 are complex, including regulation of IL-17 in melanoma by CYP11A1-derived vitamin D3 hydroxyderivatives and transcriptional regulation of IL-17 by RORγ [ 648 , 649 ].…”

Section: Role Of Vitamin D In Melanomamentioning

confidence: 99%

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

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Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and a high mortality rate. This review discusses etiologic and risk factors for melanoma, diagnostic and prognostic tools, including recent advances in molecular biology, omics, and bioinformatics, and provides an overview of its therapy. Since the incidence of melanoma is rising and mortality remains unacceptably high, we discuss its inherent properties, including melanogenesis, that make this disease resilient to treatment and propose to use AI to solve the above complex and multidimensional problems. We provide an overview on vitamin D and its anticancerogenic properties, and report recent advances in this field that can provide solutions for the prevention and/or therapy of melanoma. Experimental papers and clinicopathological studies on the role of vitamin D status and signaling pathways initiated by its active metabolites in melanoma prognosis and therapy are reviewed. We conclude that vitamin D signaling, defined by specific nuclear receptors and selective activation by specific vitamin D hydroxyderivatives, can provide a benefit for new or existing therapeutic approaches. We propose to target vitamin D signaling with the use of computational biology and AI tools to provide a solution to the melanoma problem.

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Section: Role Of Vitamin D In Melanomamentioning

confidence: 99%

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Slominski,

Kim,

Janjetovic

et al. 2024

Cancers

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“…Recently, we also showed that 20(OH)D 3 , 20,23(OH) 2 D 3 and their metabolites, that were generated by alternative pathway, can act as inverse agonists on retinoic acid-related orphan receptors, RORα and RORγ [ 100 , 101 , 102 ], which belong to the ROR subfamily of nuclear receptors, that play a crucial role in the variety of physiological processes, including immune functions [ 103 , 104 , 105 ]. In addition, lumisterol hydroxyderivatives act as inverse agonists on RORs [ 97 ].…”

Section: Vitamin D Endocrine Systemmentioning

confidence: 99%

“…Thus, there is more than one bioactive form of vitamin D and several additional to the VDR nuclear receptors that are activated by these compounds [ 36 ]. In addition, it has been documented that lumisterol, a photoderivative of vitamin D 3 , can be activated to the biologically active hydroxyderivatives that would act on LXRs and RORs to exert their phenotypic effect [ 97 , 105 , 108 , 109 ]. Vitamin D and lumisterol hydroxyderivatives can also interact with SARS-CoV-2 replication machinery enzymes [ 110 ] and angiotensin-converting enzyme 2 (ACE2) and TMPRSS2 [ 111 ] and their protective role in COVID-19 has been discussed [ 112 ].…”

Section: Vitamin D Endocrine Systemmentioning

confidence: 99%

Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy

Brożyna

Slominski

Nedoszytko

et al. 2022

IJMS

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Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2–3% of the world’s population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis.

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Retinoic Acid-Related Orphan Receptor (ROR) Inverse Agonists: Potential Therapeutic Strategies for Multiple Inflammatory Diseases?

Cited by 2 publications

References 174 publications

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Malignant Melanoma: An Overview, New Perspectives, and Vitamin D Signaling

Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy

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