Rosenkranz A A, Slastnikova T A, Durymanov M O, Sobolev A S
Institute of Gene Biology, Russian Academy of Sciences, Moscow, 199334, Russia.
Biochemistry (Mosc). 2013 Nov;78(11):1228-37. doi: 10.1134/S0006297913110035.
The conventional chemotherapeutic treatment of malignant melanoma still remains poorly efficient in most cases. Thus the use of specific features of these tumors for development of new therapeutic modalities is highly needed. Melanocortin 1 receptor (MC1R) overexpression on the cell surface of the vast majority of human melanomas, making MC1R a valuable marker of these tumors, is one of these features. Naturally, MC1R plays a key role in skin protection against damaging ultraviolet radiation by regulating eumelanin production. MC1R activation is involved in regulation of melanocyte cell division. This article reviews the peculiarities of regulation and expression of MC1R, melanocytes, and melanoma cells, along with the possible connection of MC1R with signaling pathways regulating proliferation of tumor cells. MC1R is a cell surface endocytic receptor, thus considered perspective for diagnostics and targeted drug delivery. A number of new therapeutic approaches that utilize MC1R, including endoradiotherapy with Auger electron and α- and β-particle emitters, photodynamic therapy, and gene therapy are now being developed.
在大多数情况下,恶性黑色素瘤的传统化疗治疗效果仍然不佳。因此,迫切需要利用这些肿瘤的特定特征来开发新的治疗方法。绝大多数人类黑色素瘤细胞表面存在黑皮质素1受体(MC1R)过表达,这使得MC1R成为这些肿瘤的一个有价值的标志物,这就是其中一个特征。自然地,MC1R通过调节真黑素的产生在皮肤抵御紫外线损伤方面发挥关键作用。MC1R的激活参与黑素细胞的细胞分裂调节。本文综述了MC1R、黑素细胞和黑色素瘤细胞的调节及表达特点,以及MC1R与调节肿瘤细胞增殖的信号通路之间可能存在的联系。MC1R是一种细胞表面内吞受体,因此被认为在诊断和靶向药物递送方面具有前景。目前正在开发多种利用MC1R的新治疗方法,包括使用俄歇电子以及α和β粒子发射体的内放射治疗、光动力疗法和基因疗法。