The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma
Melanoma is the malignant transformation of melanocytes and represents the most lethal form of skin cancer. While early-stage melanoma localized to the skin can be cured with surgical excision, metastatic melanoma often requires a multi-pronged approach and even then can exhibit treatment resistance...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-10-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.743667/full |
| _version_ | 1818728239634317312 |
|---|---|
| author | Alyssa L. Becker Alyssa L. Becker Evan L. Carpenter Andrzej T. Slominski Andrzej T. Slominski Arup K. Indra Arup K. Indra Arup K. Indra Arup K. Indra Arup K. Indra |
| author_facet | Alyssa L. Becker Alyssa L. Becker Evan L. Carpenter Andrzej T. Slominski Andrzej T. Slominski Arup K. Indra Arup K. Indra Arup K. Indra Arup K. Indra Arup K. Indra |
| author_sort | Alyssa L. Becker |
| collection | DOAJ |
| description | Melanoma is the malignant transformation of melanocytes and represents the most lethal form of skin cancer. While early-stage melanoma localized to the skin can be cured with surgical excision, metastatic melanoma often requires a multi-pronged approach and even then can exhibit treatment resistance. Understanding the molecular mechanisms involved in the pathogenesis of melanoma could lead to novel diagnostic, prognostic, and therapeutic strategies to ultimately decrease morbidity and mortality. One emerging candidate that may have value as both a prognostic marker and in a therapeutic context is the vitamin D receptor (VDR). VDR is a nuclear steroid hormone receptor activated by 1,25 dihydroxy-vitamin D3 [calcitriol, 1,25(OH)2D3]. While 1,25 dihydroxy-vitamin D3 is typically thought of in relation to calcium metabolism, it also plays an important role in cell proliferation, differentiation, programmed-cell death as well as photoprotection. This review discusses the role of VDR in the crosstalk between keratinocytes and melanocytes during melanomagenesis and summarizes the clinical data regarding VDR polymorphisms, VDR as a prognostic marker, and potential uses of vitamin D and its analogs as an adjuvant treatment for melanoma. |
| first_indexed | 2024-12-17T22:26:50Z |
| format | Article |
| id | doaj.art-f248b1fc757d495fbb2a2f25b1fdcb2c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-17T22:26:50Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f248b1fc757d495fbb2a2f25b1fdcb2c2022-12-21T21:30:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-10-011110.3389/fonc.2021.743667743667The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous MelanomaAlyssa L. Becker0Alyssa L. Becker1Evan L. Carpenter2Andrzej T. Slominski3Andrzej T. Slominski4Arup K. Indra5Arup K. Indra6Arup K. Indra7Arup K. Indra8Arup K. Indra9Department of Pharmaceutical Sciences, College of Pharmacy, OSU, Corvallis, OR, United StatesJohn A. Burns School of Medicine at the University of Hawai’i at Mānoa, Honolulu, HI, United StatesDepartment of Pharmaceutical Sciences, College of Pharmacy, OSU, Corvallis, OR, United StatesDepartment of Dermatology, University of Alabama at Birmingham, Birmingham, AL, United StatesCancer Chemoprevention Program, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, United StatesDepartment of Pharmaceutical Sciences, College of Pharmacy, OSU, Corvallis, OR, United StatesKnight Cancer Institute, Oregon Health & Science University (OHSU), Portland, OR, United StatesDepartment of Biochemistry and Biophysics, Oregon State University (OSU), Corvallis, OR, United StatesLinus Pauling Science Center, Oregon State University (OSU), Corvallis, OR, United StatesDepartment of Dermatology, Oregon Health & Science University (OHSU), Portland, OR, United StatesMelanoma is the malignant transformation of melanocytes and represents the most lethal form of skin cancer. While early-stage melanoma localized to the skin can be cured with surgical excision, metastatic melanoma often requires a multi-pronged approach and even then can exhibit treatment resistance. Understanding the molecular mechanisms involved in the pathogenesis of melanoma could lead to novel diagnostic, prognostic, and therapeutic strategies to ultimately decrease morbidity and mortality. One emerging candidate that may have value as both a prognostic marker and in a therapeutic context is the vitamin D receptor (VDR). VDR is a nuclear steroid hormone receptor activated by 1,25 dihydroxy-vitamin D3 [calcitriol, 1,25(OH)2D3]. While 1,25 dihydroxy-vitamin D3 is typically thought of in relation to calcium metabolism, it also plays an important role in cell proliferation, differentiation, programmed-cell death as well as photoprotection. This review discusses the role of VDR in the crosstalk between keratinocytes and melanocytes during melanomagenesis and summarizes the clinical data regarding VDR polymorphisms, VDR as a prognostic marker, and potential uses of vitamin D and its analogs as an adjuvant treatment for melanoma.https://www.frontiersin.org/articles/10.3389/fonc.2021.743667/fullmelanomavitamin D receptor (VDR)vitamin D3 metabolitetherapypathogenesistumor microenvironment |
| spellingShingle | Alyssa L. Becker Alyssa L. Becker Evan L. Carpenter Andrzej T. Slominski Andrzej T. Slominski Arup K. Indra Arup K. Indra Arup K. Indra Arup K. Indra Arup K. Indra The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma Frontiers in Oncology melanoma vitamin D receptor (VDR) vitamin D3 metabolite therapy pathogenesis tumor microenvironment |
| title | The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma |
| title_full | The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma |
| title_fullStr | The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma |
| title_full_unstemmed | The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma |
| title_short | The Role of the Vitamin D Receptor in the Pathogenesis, Prognosis, and Treatment of Cutaneous Melanoma |
| title_sort | role of the vitamin d receptor in the pathogenesis prognosis and treatment of cutaneous melanoma |
| topic | melanoma vitamin D receptor (VDR) vitamin D3 metabolite therapy pathogenesis tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.743667/full |
| work_keys_str_mv | AT alyssalbecker theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT alyssalbecker theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT evanlcarpenter theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT andrzejtslominski theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT andrzejtslominski theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra theroleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT alyssalbecker roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT alyssalbecker roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT evanlcarpenter roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT andrzejtslominski roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT andrzejtslominski roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma AT arupkindra roleofthevitamindreceptorinthepathogenesisprognosisandtreatmentofcutaneousmelanoma |