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细胞周期蛋白依赖性激酶 7(CDK7)抑制剂作为不同分子类型乳腺癌的一种新的治疗策略。

Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.

机构信息

Department of Breast Cancer, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510120, China.

出版信息

Br J Cancer. 2024 May;130(8):1239-1248. doi: 10.1038/s41416-024-02589-8. Epub 2024 Feb 14.

Abstract

BACKGROUND

Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies.

METHODS

In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer.

RESULTS

Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging.

CONCLUSION

CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

摘要

背景

细胞周期蛋白依赖性激酶(CDK)7 在许多类型的癌症中过度表达,由于其在转录和细胞周期进展中的双重作用,它是癌症治疗的一个有吸引力的靶点。此外,CDK7 可以直接调节雌激素受体(ER)的活性,ER 是乳腺癌的主要驱动因素。在临床前研究中,乳腺癌细胞对 CDK7 抑制表现出高度敏感性。

方法

在这篇综述中,我们全面总结了 CDK7 生物学的最新见解和 CDK7 抑制剂在乳腺癌治疗方面的最新进展。我们还讨论了 CDK7 抑制剂在不同分子类型乳腺癌中的当前应用,为乳腺癌的治疗提供了潜在的策略。

结果

在开发选择性 CDK7 抑制剂方面取得了显著进展,这些抑制剂在三阴性乳腺癌(TNBC)和激素受体阳性乳腺癌(HR+)中均显示出疗效。此外,与其他药物联合使用时,CDK7 抑制剂可能为内分泌治疗和化疗提供协同作用。因此,开发有效 CDK7 抑制剂并研究其在乳腺癌治疗中的应用的高质量研究正在迅速涌现。

结论

CDK7 抑制剂已成为一种有前途的治疗策略,在不同亚型的乳腺癌中表现出显著的抗癌活性,特别是那些对现有治疗方法产生耐药性的乳腺癌。

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