Ni Chun-Xiao, Xu Jia-Ju, Pang Yu, Xu Jia-Ju
Department of Minimally Invasive Oncology, Tai'an Central Hospital Affiliated to Qingdao University, Tai'an 271000, Shandong Province, China.
Department of Pediatrics, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai 264000, Shandong Province, China.
World J Clin Oncol. 2025 May 24;16(5):104623. doi: 10.5306/wjco.v16.i5.104623.
Triple negative breast cancer (TNBC) is an exceptionally aggressive subtype of breast cancer with a poor prognosis. TNBC patients have limited treatment options beyond conventional chemotherapy, and they face significant challenges associated with disease recurrence and resistance to chemotherapy. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway plays a pivotal role in cell proliferation, growth, metabolism, and survival. Its aberrant activation is closely linked to the development and progression of TNBC, as well as treatment response and drug resistance. Currently, numerous targeted drugs specifically inhibiting this signaling pathway are being developed and undergoing clinical trials. These include inhibitors targeting PI3K, AKT, or mTOR individually, as well as dual-target or multi-target inhibitors simultaneously targeting different components of this pathway. Encouragingly, some inhibitors have demonstrated promising potential in clinical trials. This review delves into the therapeutic potential of the PI3K/AKT/mTOR signaling pathway for TNBC and explores prospects for drug discovery.
三阴性乳腺癌(TNBC)是一种侵袭性极强的乳腺癌亚型,预后较差。TNBC患者除了传统化疗外,治疗选择有限,且面临疾病复发和化疗耐药相关的重大挑战。磷酸肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路在细胞增殖、生长、代谢和存活中起关键作用。其异常激活与TNBC的发生发展、治疗反应及耐药密切相关。目前,许多特异性抑制该信号通路的靶向药物正在研发并进行临床试验。这些药物包括单独靶向PI3K、AKT或mTOR的抑制剂,以及同时靶向该通路不同组分的双靶点或多靶点抑制剂。令人鼓舞的是,一些抑制剂在临床试验中已显示出有前景的潜力。本综述深入探讨了PI3K/AKT/mTOR信号通路对TNBC的治疗潜力,并探索药物研发前景。
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