Jiang Yu, Tang Zihua, Zheng Wenyue, Xiao Xue
West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Department of Pediatric Dentistry, West China Second University Hospital, Sichuan University, Chengdu, China.
Future Med Chem. 2025 Jul;17(14):1787-1813. doi: 10.1080/17568919.2025.2542720. Epub 2025 Aug 8.
Breast cancer (BC) is characterized by the abnormal and rapid growth of breast epithelial cells, driven by various carcinogenic factors. Advances in understanding the signaling pathways and molecular mechanisms involved in BC progression have facilitated the development of small molecule inhibitors for its treatment. Significant progress has been made in creating inhibitors that target the PI3K/AKT/mTOR signaling pathway. Current clinical research focuses on compounds such as GDC-0077 and NVP-BKM120, advancing into phase II/III clinical trials. Preclinical drugs like NVP-CLR457, AZD6482, PF-06843195, and GDC-0326 show promising potential for further optimization and entry into BC clinical trials. This review aims to provide an overview of the clinical and preclinical development of small molecule inhibitors for various molecular subtypes of BC, emphasizing their structural composition, therapeutic outcomes, and mechanisms of action. Additionally, we highlight key targets and pathways involved in BC pathogenesis, offering essential insights for the design of effective therapeutic agents for breast cancer.
乳腺癌（BC）的特征是乳腺上皮细胞在各种致癌因素的驱动下异常快速生长。对BC进展过程中涉及的信号通路和分子机制的理解取得了进展，这促进了用于其治疗的小分子抑制剂的开发。在开发靶向PI3K/AKT/mTOR信号通路的抑制剂方面取得了重大进展。目前的临床研究集中在GDC-0077和NVP-BKM120等化合物上，已进入II/III期临床试验。像NVP-CLR457、AZD6482、PF-06843195和GDC-0326等临床前药物显示出进一步优化并进入BC临床试验的潜力。本综述旨在概述针对BC各种分子亚型的小分子抑制剂的临床和临床前开发情况，重点介绍其结构组成、治疗效果和作用机制。此外，我们强调了BC发病机制中涉及的关键靶点和途径，为设计有效的乳腺癌治疗药物提供了重要见解。
