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用于治疗脑膜瘤的细胞周期蛋白依赖性激酶4/6抑制剂

CDK 4/6 inhibitors for the treatment of meningioma.

作者信息

Young Jacob S, Kidwell Reilly L, Zheng Allison, Haddad Alex F, Aghi Manish K, Raleigh David R, Schulte Jessica D, Butowski Nicholas A

机构信息

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States.

Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, United States.

出版信息

Front Oncol. 2022 Jul 22;12:931371. doi: 10.3389/fonc.2022.931371. eCollection 2022.

Abstract

Meningiomas are the most common non-metastatic brain tumors, and although the majority are relatively slow-growing and histologically benign, a subset of meningiomas are aggressive and remain challenging to treat. Despite a standard of care that includes surgical resection and radiotherapy, and recent advances in meningioma molecular grouping, there are no systemic medical options for patients with meningiomas that are resistant to standard interventions. Misactivation of the cell cycle at the level of CDK4/6 is common in high-grade or molecularly aggressive meningiomas, and CDK4/6 has emerged as a potential target for systemic meningioma treatments. In this review, we describe the preclinical evidence for CDK4/6 inhibitors as a treatment for high-grade meningiomas and summarize evolving clinical experience with these agents. Further, we highlight upcoming clinical trials for patients meningiomas, and discuss future directions aimed at optimizing the efficacy of these therapies and selecting patients most likely to benefit from their use.

摘要

脑膜瘤是最常见的非转移性脑肿瘤,尽管大多数脑膜瘤生长相对缓慢且组织学上为良性,但有一部分脑膜瘤具有侵袭性,治疗仍然具有挑战性。尽管目前的标准治疗包括手术切除和放疗,并且脑膜瘤分子分型也有了最新进展,但对于对标准干预措施耐药的脑膜瘤患者,尚无全身性药物治疗选择。细胞周期蛋白依赖性激酶4/6(CDK4/6)水平的细胞周期异常激活在高级别或分子侵袭性脑膜瘤中很常见,CDK4/6已成为全身性脑膜瘤治疗的潜在靶点。在这篇综述中,我们描述了CDK4/6抑制剂治疗高级别脑膜瘤的临床前证据,并总结了这些药物不断发展的临床经验。此外,我们强调了即将开展的针对脑膜瘤患者的临床试验,并讨论了旨在优化这些治疗效果以及选择最可能从其使用中获益的患者的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d9b/9354681/f9961f33d6c0/fonc-12-931371-g001.jpg

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