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CDK4/6抑制剂在乳腺癌当前治疗中的最新进展

Recent progress of CDK4/6 inhibitors' current practice in breast cancer.

作者信息

Wang Xueqing, Zhao Shanshan, Xin Qinghan, Zhang Yunkun, Wang Kainan, Li Man

机构信息

Department of Oncology, the Second Hospital of Dalian Medical University, Dalian, China.

Department of Breast Surgery, Dalian Municipal Central Hospital, Dalian, China.

出版信息

Cancer Gene Ther. 2024 Sep;31(9):1283-1291. doi: 10.1038/s41417-024-00747-x. Epub 2024 Feb 26.

Abstract

Dysregulated cellular proliferation represents a hallmark feature across all cancers. Aberrant activation of the cyclin-dependent kinase 4 and 6 (CDK4/6) pathway, independent of mitogenic signaling, engenders uncontrolled breast cancer cell proliferation. Consequently, the advent of CDK4/6 inhibition has constituted a pivotal milestone in the realm of targeted breast cancer therapy. The combination of CDK4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) has emerged as the foremost therapeutic modality for patients afflicted with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer. At present, the Food and Drug Administration (FDA) has sanctioned various CDK4/6i for employment as the primary treatment regimen in HR + /HER2- breast cancer. This therapeutic approach has demonstrated a substantial extension of progression-free survival (PFS), often amounting to several months, when administered alongside endocrine therapy. Within this comprehensive review, we systematically evaluate the utilization strategies of CDK4/6i across various subpopulations of breast cancer and explore potential therapeutic avenues following disease progression during application of CDK4/6i therapy.

摘要

细胞增殖失调是所有癌症的一个标志性特征。细胞周期蛋白依赖性激酶4和6(CDK4/6)通路的异常激活,不依赖于有丝分裂信号,导致乳腺癌细胞不受控制地增殖。因此,CDK4/6抑制的出现已成为靶向乳腺癌治疗领域的一个关键里程碑。CDK4/6抑制剂(CDK4/6i)与内分泌治疗(ET)的联合应用已成为激素受体阳性(HR+)/人表皮生长因子受体2阴性(HER2-)晚期乳腺癌患者的首要治疗方式。目前,美国食品药品监督管理局(FDA)已批准多种CDK4/6i作为HR+/HER2-乳腺癌的主要治疗方案。当与内分泌治疗联合使用时,这种治疗方法已证明无进展生存期(PFS)有显著延长,通常可达数月。在这篇全面的综述中,我们系统地评估了CDK4/6i在乳腺癌各亚群中的应用策略,并探讨了在CDK4/6i治疗期间疾病进展后的潜在治疗途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4c4/11405274/1fed0d2a5528/41417_2024_747_Fig1_HTML.jpg

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