文章：

三阴性乳腺癌与新兴治疗策略：ATR与CHK1/2作为潜在靶点

Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets

原文发布日期：13 March 2024

DOI: 10.3390/cancers16061139

类型: Article

开放获取: 是

英文摘要：

Worldwide, breast cancer is the most frequently diagnosed malignancy in women, with triple-negative breast cancer (TNBC) being the most aggressive molecular subtype. Due to the dearth of effective therapeutic options for TNBC, novel agents targeting key mechanisms and pathways in cancer cells are continuously explored; these include ATR inhibitors, which target the ATR kinase involved in the DNA damage response (DDR) pathway, and CHK1/2 inhibitors, which target the Checkpoint Kinase 1/2 (CHK1/2) involved in cell cycle arrest and DNA repair. ATR and CHK1/2 inhibitors show potential as prospective treatments for TNBC by focusing on the DDR and interfering with cell cycle regulation in cancer cells. Preliminary preclinical and clinical findings suggest that when combined with chemotherapy, ATR and CHK1/2 inhibitors demonstrate significant anti-proliferative efficacy against TNBC. In this article, we introduce ATR and CHK1/2 inhibitors as promising therapeutic approaches for the management of TNBC. Preclinical and clinical studies performed evaluating ATR and CHK1/2 inhibitors for the treatment of TNBC and associated challenges encountered in this context to date are reviewed.

摘要翻译： 

在全球范围内，乳腺癌是女性最常见的恶性肿瘤，其中三阴性乳腺癌（TNBC）是最具侵袭性的分子亚型。由于TNBC缺乏有效的治疗选择，针对癌细胞关键机制和通路的新型药物不断被探索；这些包括靶向DNA损伤反应（DDR）通路中ATR激酶的ATR抑制剂，以及靶向参与细胞周期停滞和DNA修复的检查点激酶1/2（CHK1/2）的CHK1/2抑制剂。ATR和CHK1/2抑制剂通过聚焦于DDR并干扰癌细胞的细胞周期调控，显示出作为TNBC潜在治疗手段的前景。初步的临床前和临床研究结果表明，当与化疗联合使用时，ATR和CHK1/2抑制剂对TNBC表现出显著的抗增殖效果。本文介绍了ATR和CHK1/2抑制剂作为治疗TNBC的有前景的治疗方法。综述了迄今为止评估ATR和CHK1/2抑制剂治疗TNBC的临床前和临床研究，以及在此背景下遇到的挑战。

原文链接：

Triple-Negative Breast Cancer and Emerging Therapeutic Strategies: ATR and CHK1/2 as Promising Targets