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靶向脂肪肉瘤中的 CDK4(细胞周期蛋白依赖性激酶)扩增:全面综述。

Targeting CDK4 (cyclin-dependent kinase) amplification in liposarcoma: A comprehensive review.

机构信息

Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.

Department of Hematology-Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.

出版信息

Crit Rev Oncol Hematol. 2020 Sep;153:103029. doi: 10.1016/j.critrevonc.2020.103029. Epub 2020 Jun 18.

Abstract

Well-differentiated/dedifferentiated (WD/DD) liposarcomas, the most common form of liposarcomas, constitute up to 20 % of all soft tissue sarcomas. Several oncogenes are thought to be involved in liposarcoma pathogenesis, mainly MDM2, CDK4 and HMGA2. While MDM2 inhibitors are now tested in clinical trials, a second actionable and promising target appears to be cyclin-dependent kinase 4 (CDK4), which is amplified in up to 90 % of well differentiated or dedifferentiated (WD/DD) liposarcoma. With the paucity of available therapeutic options, the inhibition of CDK4 represent a potential therapeutic option. In this paper, we review the role of CDK4/6 inhibitors in targeting the commonly identified CDK4 amplification in WD/DD liposarcoma, with an emphasis on the published and currently ongoing trials.

摘要

高分化/去分化(WD/DD)脂肪肉瘤是最常见的脂肪肉瘤类型,占所有软组织肉瘤的 20%。几种癌基因被认为与脂肪肉瘤的发病机制有关,主要有 MDM2、CDK4 和 HMGA2。虽然 MDM2 抑制剂目前正在临床试验中进行测试,但第二个可行且有前途的靶点似乎是细胞周期蛋白依赖性激酶 4(CDK4),其在高达 90%的高分化或去分化(WD/DD)脂肪肉瘤中被扩增。鉴于可用的治疗选择有限,抑制 CDK4 代表了一种潜在的治疗选择。本文重点介绍了已发表的和正在进行的临床试验,综述了 CDK4/6 抑制剂在针对 WD/DD 脂肪肉瘤中常见的 CDK4 扩增的作用。

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