文章：

黑色素瘤细胞周期靶向治疗的最新进展

Recent Developments in Targeting the Cell Cycle in Melanoma

原文发布日期：11 April 2025

DOI: 10.3390/cancers17081291

类型: Article

开放获取: 是

英文摘要：

Melanoma is an aggressive cancer with rising incidence, particularly among older individuals. Despite advancements in targeted therapies for BRAF and MEK proteins and immunotherapies, many patients either fail to respond or develop resistance. For those progressing on immunotherapy, limited treatment options remain. The Cyclin D–CDK4/6–RB pathway is commonly dysregulated in melanoma, with up to 90% of cases showing alterations that activate it. Although targeting Cyclin–CDK complexes has shown promise in preclinical models, clinical responses have been suboptimal. This review explores the molecular mechanisms behind Cyclin–CDK dysregulation in melanoma and the challenges of targeting this pathway. It also discusses strategies to improve the efficacy of CDK4/6 inhibitors, including combination therapies to overcome resistance and enhance patient outcomes. Understanding these mechanisms can guide the development of more effective treatments for melanoma.

摘要翻译： 

黑色素瘤是一种侵袭性癌症，其发病率持续上升，尤其在老年人群中更为显著。尽管针对BRAF和MEK蛋白的靶向治疗及免疫疗法已取得进展，但许多患者仍存在治疗无效或产生耐药性的问题。对于免疫治疗进展的患者，目前治疗选择十分有限。细胞周期蛋白D–CDK4/6–RB通路在黑色素瘤中普遍失调，高达90%的病例存在激活该通路的基因改变。尽管靶向细胞周期蛋白–CDK复合物在临床前模型中显示出潜力，但临床疗效尚未达到理想状态。本综述探讨了黑色素瘤中细胞周期蛋白–CDK失调的分子机制及靶向该通路面临的挑战，并讨论了提升CDK4/6抑制剂疗效的策略，包括通过联合疗法克服耐药性以改善患者预后。深入理解这些机制将有助于开发更有效的黑色素瘤治疗方案。

原文链接：

Recent Developments in Targeting the Cell Cycle in Melanoma