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阿贝西利治疗子宫内膜癌的前景。

Therapeutic Prospects of Abemaciclib for Patients with Endometrial Cancer.

机构信息

Gynecologic Oncology Program, AdventHealth Cancer Institute, Orlando, FL 32804, USA.

出版信息

Curr Oncol. 2024 Sep 12;31(9):5374-5383. doi: 10.3390/curroncol31090397.

DOI:10.3390/curroncol31090397
PMID:39330025
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11431580/
Abstract

Endometrial cancer (EC) is a common gynecologic malignancy with a rising incidence due to obesity, comorbid conditions, and related lifestyle factors. The standard of care for primary disease consists of surgical resection with/without chemotherapy ± radiotherapy for select patients. Recurrence is common in patients with advanced-stage disease and/or high-risk features, who primarily are treated with systemic therapy. The identification of novel targets in malignant EC has led to the development of wide-range inhibitors. Abemaciclib is an orally active unique cyclin-dependent kinase (CDK) inhibitor, selective for the CDK4 and CDK6 cell cycle pathways. This agent has potential anti-neoplastic activity and is indicated in combination with various therapies such as endocrine therapy, aromatase inhibitors, and hormone therapies, primarily in breast cancer (BC). Herein, we sought to summarize the biochemical/pharmacological properties of abemaciclib and its therapeutic potential in EC. While the therapeutic role(s) of abemaciclib was fairly established in a subset of patients with advanced/metastatic BC through the pivotal MONARCH trials, its attributes and clinical utility in EC are limited. Thus, based on some promising pre-clinical/translational insights and a recent phase II study, we highlight abemaciclib's properties and potential clinical usefulness in patients with EC, particularly in recurrent estrogen-receptor-positive cases.

摘要

子宫内膜癌 (EC) 是一种常见的妇科恶性肿瘤,由于肥胖、合并症和相关生活方式因素,发病率呈上升趋势。原发性疾病的标准治疗包括手术切除,选择性患者加用化疗±放疗。晚期疾病和/或高危特征的患者复发常见,主要采用全身治疗。恶性 EC 中新型靶标的鉴定导致了广泛抑制剂的发展。阿贝西利是一种口服活性的独特细胞周期蛋白依赖性激酶 (CDK) 抑制剂,对 CDK4 和 CDK6 细胞周期途径具有选择性。该药物具有潜在的抗肿瘤活性,并与各种治疗方法联合应用,如内分泌治疗、芳香酶抑制剂和激素治疗,主要用于乳腺癌 (BC)。在此,我们旨在总结阿贝西利的生化/药理学特性及其在 EC 中的治疗潜力。虽然通过关键性 MONARCH 试验,阿贝西利在一部分晚期/转移性 BC 患者中的治疗作用已得到充分证实,但它在 EC 中的特性和临床应用有限。因此,基于一些有前景的临床前/转化研究和最近的一项 II 期研究,我们强调了阿贝西利在 EC 患者中的特性和潜在临床应用价值,特别是在复发性雌激素受体阳性病例中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/b15557670848/curroncol-31-00397-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/840577c51f3a/curroncol-31-00397-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/58f8e157447d/curroncol-31-00397-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/0c17c6becfd0/curroncol-31-00397-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/d4121dd69890/curroncol-31-00397-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/b15557670848/curroncol-31-00397-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/840577c51f3a/curroncol-31-00397-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/58f8e157447d/curroncol-31-00397-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/0c17c6becfd0/curroncol-31-00397-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/d4121dd69890/curroncol-31-00397-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20c5/11431580/b15557670848/curroncol-31-00397-g005.jpg

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