磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B (AKT/PKB)/哺乳动物雷帕霉素靶蛋白(mTOR)信号传导通路可抑制肿瘤细胞凋亡、促进细胞生存、调节细胞周期,促进肿瘤新生血管的形成以及侵袭与转移,在肿瘤的发生、发展、治疗及转归中发挥着重要作用.而近来研究发现此信号通路与乳腺癌的关系非常密切,使之成为乳腺癌新的治疗靶点及研究热点.临床前研究已经证实,PI3K抑制剂及mTOR抑制剂通过不同的作用靶点作用于PI3K/AKT/mTOR信号传导通路上,从而达到抗癌的作用.PI3K抑制剂中有些药物只作用于PI3K靶点,有些作用于PI3K和mTOR双靶点,且现阶段的研究更倾向于进行针对不同PI3K亚型的分子靶向药物的研究,以达到对PI3K通路的抑制作用更具有针对性和特异性的目的,其在临床上的作用和疗效需要进行进一步的研究.而mTOR抑制剂针对的作用靶点是mTORC1,是PI3K/AKT/mTOR通路中开发较为完善的分子靶向药物,雷帕霉素衍生物类药物已经在乳腺癌中进行Ⅱ/Ⅲ期临床试验,且该类药物在联合乳腺癌内分泌治疗药物或人表皮生长因子受体-2(Her-2)靶向治疗药物治疗转移性乳腺癌中取得了良好的疗效.%The PI3K/AKT/mTOR signaling pathway is involved in the inhibition of tumor cell apoptosis, the promo-tion of cell survival, cell cycle regulation, tumor angiogenesis, invasion and metastasis and therefore plays an important role in tumorigenesis, tumor growth, tumor treatment and patients' prognosis. Recent studies showed this signaling pathway is closely related to breast cancer, making it a new therapeutic target and a hotspot in breast cancer research. Pre - clinical studies have confirmed that PI3K inhibitors and mTOR inhibitors achieve anticancer effects by targeting different targets of the PI3K/AKT/mT0R signaling pathway. Among the PI3K inhibitors, some medicines only target PI3K, whereas others target both PI3K and mTOR. Currently, researchers tend to focus on molecular targets based on different PI3K subtypes to achieve more targeted and specific inhibition of the PI3K pathway. However, the clinical efficacy and efficiency of these inhibitors need to be further studied. The mTOR inhibitors target mTORCl and have been become relatively well - developed targeted therapies for the PI3K/AKT/ mTOR pathway. Rapamycin derivatives have been studied in phase Ⅱ/Ⅲ clinical trials in breast cancer, and these derivatives a-chieved positive results in the treatment of metastatic breast cancer when combined with endocrine therapy or Her - 2 - targeted therapies.
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