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细胞周期蛋白依赖性激酶抑制剂在罕见黑素瘤亚型治疗中的应用。

Cyclin-Dependent Kinase Inhibitors in the Rare Subtypes of Melanoma Therapy.

机构信息

Vascular Biology Student Research Club, Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland.

Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, Poland.

出版信息

Molecules. 2024 Nov 6;29(22):5239. doi: 10.3390/molecules29225239.

Abstract

Melanoma occurs in various forms and body areas, not only in the cutis, but also in mucous membranes and the uvea. Rarer subtypes of that cancer differ in genomic aberrations, which cause their minor sensibility to regular cutaneous melanoma therapies. Therefore, it is essential to discover new strategies for treating rare forms of melanoma. In recent years, interest in applying CDK inhibitors (CDKIs) in cancer therapy has grown, as they are able to arrest the cell cycle and inhibit cell proliferation. Current studies highlight selective CDK4/6 inhibitors, like palbociclib or abemaciclib, as a very promising therapeutic option, since they were accepted by the FDA for advanced breast cancer treatment. However, cells of every subtype of melanoma do not react to CDKIs the same way, which is partly because of the genetic differences between them. Herein, we discuss the past and current research relevant to targeting various CDKs in mucosal, uveal and acral melanomas. We also briefly describe the issue of amelanotic and desmoplastic types of melanoma and the need to do more research to discover cell cycle dysregulations, which cause the growth of the mentioned forms of cancer.

摘要

黑色素瘤有多种形式和发生部位,不仅发生于皮肤,也可发生于黏膜和葡萄膜。这种癌症的罕见亚型在基因组异常方面存在差异,这导致它们对常规皮肤黑色素瘤治疗的敏感性降低。因此,发现治疗罕见类型黑色素瘤的新策略至关重要。近年来,人们对应用细胞周期蛋白依赖性激酶抑制剂(CDKIs)治疗癌症的兴趣日益浓厚,因为它们能够使细胞周期停滞并抑制细胞增殖。目前的研究强调了选择性 CDK4/6 抑制剂(如 palbociclib 或 abemaciclib)作为一种很有前途的治疗选择,因为它们已被 FDA 批准用于治疗晚期乳腺癌。然而,黑色素瘤的每种亚型的细胞对 CDKIs 的反应并不相同,这部分是由于它们之间的遗传差异。本文讨论了针对黏膜、葡萄膜和肢端黑色素瘤中各种 CDK 的过去和当前研究。我们还简要描述了无黑色素性和促结缔组织增生性黑色素瘤的问题,并需要进行更多的研究以发现导致上述癌症生长的细胞周期失调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb1b/11596694/ce405aa8dc71/molecules-29-05239-g001.jpg

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