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免疫疗法在错配修复缺陷型子宫内膜癌中的作用:现状与未来展望

The Role of Immunotherapy in MMR-Deficient Endometrial Carcinoma: State of the Art and Future Perspectives.

作者信息

Marchetti Matteo, Ferrari Jacopo, Vezzaro Tommaso, Masatti Laura, Tasca Giulia, Maggino Tiziano, Tozzi Roberto, Saccardi Carlo, Noventa Marco, Spagnol Giulia

机构信息

Unit of Gynecology and Obstetrics, Department of Women and Children's Health, University of Padua, 35100 Padua, Italy.

Department of Biology, University of Padua, 35100 Padua, Italy.

出版信息

J Clin Med. 2024 Nov 21;13(23):7041. doi: 10.3390/jcm13237041.

Abstract

This study provides a comprehensive overview of the role of immunotherapy in the treatment of mismatch repair-deficient (MMRd) endometrial carcinomas. Immunotherapy has emerged as a transformative approach in the treatment of MMRd due to the high mutation rate and subsequent PD-1/PD-L1 overexpression seen in these tumors. This review analyzes the current landscape of existing randomized clinical trials, highlighting the efficacy of immune checkpoint inhibitors (ICIs) like pembrolizumab, avelumab, and dostarlimab. Additionally, the focus extends to the potential of combined therapeutic strategies, such as the integration of ICIs with targeted agents, while also exploring the application of immunotherapy in non-traditional settings beyond advanced or recurrent disease. This includes emerging roles in the adjuvant and neoadjuvant contexts to prevent recurrence and target early-stage disease. These findings underscore the importance of tailoring treatments based on the molecular characteristics of each tumor and paving the way for future advancements in the field of gynecologic oncology. Despite promising results, this article acknowledges the necessity of further research to refine patient selection criteria and explore combination strategies that can overcome resistance mechanisms.

摘要

本研究全面概述了免疫疗法在错配修复缺陷(MMRd)子宫内膜癌治疗中的作用。由于这些肿瘤中存在高突变率以及随后出现的PD-1/PD-L1过表达,免疫疗法已成为治疗MMRd的一种变革性方法。本综述分析了现有随机临床试验的现状,突出了帕博利珠单抗、阿维鲁单抗和多斯塔利单抗等免疫检查点抑制剂(ICI)的疗效。此外,重点还延伸至联合治疗策略的潜力,例如ICI与靶向药物的联合应用,同时也探讨了免疫疗法在晚期或复发性疾病以外的非传统环境中的应用。这包括在辅助和新辅助治疗中预防复发以及针对早期疾病的新作用。这些发现强调了根据每个肿瘤的分子特征定制治疗方案的重要性,并为妇科肿瘤学领域的未来进展铺平了道路。尽管取得了有前景的结果,但本文承认有必要进一步研究以完善患者选择标准,并探索能够克服耐药机制 的联合策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/705a/11642574/1257ff8c2b92/jcm-13-07041-g001.jpg

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