Hao Chunfang, Wei Yunchu, Meng Wenjing, Zhang Jie, Yang Xiaonan
Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; Tianjin Cancer Hospital Airport Hospital, Tianjin, China; National Clinical Research Center for Cancer, Tianjin, China.
Peking University Health Science Center, Beijing, China.
Cancer Treat Rev. 2025 Jan;132:102861. doi: 10.1016/j.ctrv.2024.102861. Epub 2024 Nov 19.
Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays a pivotal role in the development and progression of various cancers. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, aberrations in this pathway are increasingly recognized as key drivers of resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, the first-line treatments for this disease subtype. Recognizing the urgent need for alternative therapeutic strategies, significant advancements have been made in developing PI3K/AKT/mTOR inhibitors for HR+ advanced/metastatic breast cancer. Among these inhibitors, capivasertib and alpelisib have received approval as targeted therapies for this indication. This review provides a comprehensive summary of the latest developments in PI3K/AKT/mTOR inhibitors for HR+ breast cancer. It also delves into different aspects, including sampling, testing method and timing, of PI3K/AKT/mTOR diagnostic testing. Additionally, the review discusses key considerations for integrating these inhibitors into clinical practice, such as timing and choice of PI3K/AKT/mTOR inhibitors, and management of treatment toxicities. By examining these different aspects, this review aims to provide valuable insights into optimizing the clinical utility of PI3K/AKT/mTOR inhibitors in HR+ advanced breast cancer.
磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素哺乳动物靶点（PI3K/AKT/mTOR）信号通路的失调在多种癌症的发生和发展中起着关键作用。在激素受体阳性（HR+）/人表皮生长因子受体2阴性（HER2-）的晚期乳腺癌中，该信号通路的异常越来越被认为是对内分泌治疗和细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂耐药的关键驱动因素，而这两种药物是该疾病亚型的一线治疗药物。鉴于迫切需要替代治疗策略，在开发用于HR+晚期/转移性乳腺癌的PI3K/AKT/mTOR抑制剂方面已取得了重大进展。在这些抑制剂中，卡匹西利和阿培利司已获批用于该适应症的靶向治疗。本综述全面总结了HR+乳腺癌PI3K/AKT/mTOR抑制剂的最新进展。它还深入探讨了PI3K/AKT/mTOR诊断检测的不同方面，包括样本采集、检测方法和检测时机。此外，该综述讨论了将这些抑制剂纳入临床实践的关键考虑因素，如PI3K/AKT/mTOR抑制剂的使用时机和选择，以及治疗毒性的管理。通过审视这些不同方面，本综述旨在为优化PI3K/AKT/mTOR抑制剂在HR+晚期乳腺癌中的临床应用提供有价值的见解。
