文章：

超越抗PD-1/PD-L1疗法：提升三阴性乳腺癌中免疫检查点抑制剂的应答效果

Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer

原文发布日期：11 June 2024

DOI: 10.3390/cancers16122189

类型: Article

开放获取: 是

英文摘要：

The introduction of anti-programmed cell death protein-1 (anti-PD-1) to the clinical management of triple-negative breast cancer (TNBC) represents a breakthrough for a disease whose treatment has long relied on the standards of chemotherapy and surgery. Nevertheless, few TNBC patients achieve a durable remission in response to anti-PD-1, and there is a need to develop strategies to maximize the potential benefit of immune checkpoint inhibition (ICI) for TNBC patients. In the present review, we discuss three conceptual strategies to improve ICI response rates in TNBC patients. The first effort involves improving patient selection. We discuss proposed biomarkers of response and resistance to anti-PD-1, concluding that an optimal biomarker will likely be multifaceted. The second effort involves identifying existing targeted therapies or chemotherapies that may synergize with ICI. In particular, we describe recent efforts to use inhibitors of the PI3K/AKT or RAS/MAPK/ERK pathways in combination with ICI. Third, considering the possibility that targeting the PD-1 axis is not the most promising strategy for TNBC treatment, we describe ongoing efforts to identify novel immunotherapy strategies.

摘要翻译： 

抗程序性细胞死亡蛋白-1（抗PD-1）疗法引入三阴性乳腺癌（TNBC）的临床治疗，标志着该疾病治疗领域的重大突破，此前其治疗长期依赖于化疗和手术的标准方案。然而，仅少数TNBC患者对抗PD-1治疗能实现持久缓解，因此亟需制定策略以最大化免疫检查点抑制剂（ICI）对TNBC患者的潜在获益。本综述探讨了提升TNBC患者ICI应答率的三种策略构想。首要策略在于优化患者筛选，我们讨论了已提出的抗PD-1治疗应答与耐药生物标志物，认为理想的生物标志物应具备多维度特征。其次，致力于筛选可与ICI协同作用的现有靶向疗法或化疗方案，特别阐述了近期将PI3K/AKT或RAS/MAPK/ERK通路抑制剂与ICI联合应用的研究进展。第三，考虑到靶向PD-1轴可能并非TNBC治疗的最优策略，我们概述了当前探索新型免疫治疗方案的持续努力。

原文链接：

Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer