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临床指南与皮肤淋巴瘤的新型分子靶点

Clinical Guidelines and New Molecular Targets for Cutaneous Lymphomas.

机构信息

Department of Dermatology, International University of Health and Welfare, Chiba 286-8520, Japan.

出版信息

Int J Mol Sci. 2021 Oct 14;22(20):11079. doi: 10.3390/ijms222011079.

Abstract

Primary cutaneous lymphomas are heterogenous lymphoproliferative disorders. Some patients show rapid progression and the need for treatment of advanced disease is still unmet. The frequency of each subtype of cutaneous lymphoma varies among different ethnic groups, as do the medical systems found in different countries. It is important to know the differences in clinical guidelines in different areas of the world. Although current monochemotherapy with gemcitabine or pegylated liposomal doxorubicin is temporarily effective for mycosis funogides (MF) and Sézary syndrome (SS)-representative types of cutaneous lymphomas-the duration of response is usually limited. Therefore, treatment strategies targeting tumor-specific molecules have been developed. Molecular targets for MS/SS are currently CD30, CCR4, CD25, CD52, and histone deacetylases, most of which are surface molecules specifically expressed on tumor cells. As a result of advances in research techniques, different kinds of genomic alterations in MF/SS have been revealed. Molecular targets for MS/SS in the near future would be CD158k, JAK, PIK3, the mammalian target of rapamycin, and microRNAs, most of which mediate intracellular signaling pathways. Personalized therapy based on the detection of the genetic signatures of tumors and inhibition of the most suitable target molecules constitutes a future treatment strategy for MF/SS.

摘要

原发性皮肤淋巴瘤是异质性的淋巴增生性疾病。部分患者疾病进展迅速,仍需治疗晚期疾病。不同种族间皮肤淋巴瘤的各亚型频率不同,不同国家的医疗体系也不同。了解世界各地临床指南的差异很重要。虽然目前吉西他滨或聚乙二醇脂质体阿霉素单药化疗对蕈样霉菌病(MF)和塞扎里综合征(SS)——代表性的皮肤淋巴瘤类型——暂时有效,但反应持续时间通常有限。因此,已经开发了针对肿瘤特异性分子的治疗策略。MS/SS 的分子靶标目前为 CD30、CCR4、CD25、CD52 和组蛋白去乙酰化酶,其中大多数是肿瘤细胞特异性表达的表面分子。随着研究技术的进步,MF/SS 中的不同类型基因组改变已经被揭示。MS/SS 的分子靶标在不久的将来将是 CD158k、JAK、PIK3、哺乳动物雷帕霉素靶蛋白和 microRNAs,其中大多数介导细胞内信号通路。基于肿瘤遗传特征检测和最适合的靶标分子抑制的个体化治疗构成了 MF/SS 的未来治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd58/8537763/7494e858cf09/ijms-22-11079-g001.jpg

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