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抑制CDK4/6作为卵巢癌患者的治疗方法:当前证据与未来展望

Inhibition of CDK4/6 as Therapeutic Approach for Ovarian Cancer Patients: Current Evidences and Future Perspectives.

作者信息

Dall'Acqua Alessandra, Bartoletti Michele, Masoudi-Khoram Nastaran, Sorio Roberto, Puglisi Fabio, Belletti Barbara, Baldassarre Gustavo

机构信息

Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy.

Medical Oncology and Cancer Prevention Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy.

出版信息

Cancers (Basel). 2021 Jun 17;13(12):3035. doi: 10.3390/cancers13123035.

Abstract

Alterations in components of the cell-cycle machinery are present in essentially all tumor types. In particular, molecular alterations resulting in dysregulation of the G1 to S phase transition have been observed in almost all human tumors, including ovarian cancer. These alterations have been identified as potential therapeutic targets in several cancer types, thereby stimulating the development of small molecule inhibitors of the cyclin dependent kinases. Among these, CDK4 and CDK6 inhibitors confirmed in clinical trials that CDKs might indeed represent valid therapeutic targets in, at least some, types of cancer. CDK4 and CDK6 inhibitors are now used in clinic for the treatment of patients with estrogen receptor positive metastatic breast cancer and their clinical use is being tested in many other cancer types, alone or in combination with other agents. Here, we review the role of CDK4 and CDK6 complexes in ovarian cancer and propose the possible use of their inhibitors in the treatment of ovarian cancer patients with different types and stages of disease.

摘要

几乎所有肿瘤类型中都存在细胞周期机制组成部分的改变。特别是,在几乎所有人类肿瘤(包括卵巢癌)中都观察到了导致G1期到S期转换失调的分子改变。这些改变已被确定为几种癌症类型的潜在治疗靶点,从而推动了细胞周期蛋白依赖性激酶小分子抑制剂的开发。其中,CDK4和CDK6抑制剂在临床试验中得到证实,表明CDK在至少某些类型的癌症中可能确实是有效的治疗靶点。CDK4和CDK6抑制剂目前已在临床上用于治疗雌激素受体阳性转移性乳腺癌患者,并且它们在许多其他癌症类型中的临床应用正在单独或与其他药物联合进行测试。在此,我们综述了CDK4和CDK6复合物在卵巢癌中的作用,并提出了其抑制剂在治疗不同类型和疾病阶段的卵巢癌患者中的可能应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83aa/8235237/5b0ee54b26ac/cancers-13-03035-g001.jpg

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