Becker Alyssa L, Carpenter Evan L, Slominski Andrzej T, Indra Arup K
Department of Pharmaceutical Sciences, College of Pharmacy, OSU, Corvallis, OR, United States.
John A. Burns School of Medicine at the University of Hawai'i at Mānoa, Honolulu, HI, United States.
Front Oncol. 2021 Oct 6;11:743667. doi: 10.3389/fonc.2021.743667. eCollection 2021.
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)D3]. 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.
黑色素瘤是黑素细胞的恶性转化，是皮肤癌中最致命的一种形式。虽然局限于皮肤的早期黑色素瘤可通过手术切除治愈，但转移性黑色素瘤通常需要多管齐下的治疗方法，即便如此仍可能出现治疗抵抗。了解黑色素瘤发病机制中涉及的分子机制，可能会带来新的诊断、预后和治疗策略，最终降低发病率和死亡率。一种作为预后标志物和治疗手段可能都有价值的新兴候选物质是维生素D受体（VDR）。VDR是一种核类固醇激素受体，由1,25-二羟基维生素D3[骨化三醇，1,25(OH)D3]激活。虽然1,25-二羟基维生素D3通常被认为与钙代谢有关，但它在细胞增殖、分化、程序性细胞死亡以及光保护中也起着重要作用。本文综述了VDR在黑色素瘤发生过程中角质形成细胞与黑素细胞相互作用中的作用，并总结了关于VDR多态性、VDR作为预后标志物以及维生素D及其类似物作为黑色素瘤辅助治疗的潜在用途的临床数据。
