Holloway Ryan W, Marignani Paola A
Department of Biochemistry & Molecular Biology, Faculty of Medicine, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Cancers (Basel). 2021 Jun 11;13(12):2922. doi: 10.3390/cancers13122922.
Up to one third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mechanistic target of rapamycin (mTOR) pathway activity and a metabolic shift to glycolysis. Although inhibitors targeting the HER2 receptor have been successful in treating HER2-positive breast cancer, anti-HER2 therapy is associated with a high risk of recurrence and drug resistance due to stimulation of the PI3K-Akt-mTOR signaling pathway and glycolysis. Combination therapies against HER2 with inhibition of mTOR improve clinical outcomes compared to HER2 inhibition alone. Here, we review the role of the HER2 receptor, mTOR pathway, and glycolysis in HER2-positive breast cancer, along with signaling mechanisms and the efficacy of treatment strategies of HER2-positive breast cancer.
高达三分之一的乳腺癌被归类为侵袭性HER2阳性亚型，与HER2阴性乳腺癌相比，其复发风险更高。与该亚型相关的HER2过度活跃通过上调雷帕霉素机制靶点（mTOR）信号通路活性和向糖酵解的代谢转变来驱动肿瘤生长。尽管靶向HER2受体的抑制剂已成功用于治疗HER2阳性乳腺癌，但由于刺激PI3K-Akt-mTOR信号通路和糖酵解，抗HER2治疗与高复发风险和耐药性相关。与单独抑制HER2相比，联合抑制HER2和mTOR的疗法可改善临床结局。在此，我们综述HER2受体、mTOR信号通路和糖酵解在HER2阳性乳腺癌中的作用，以及HER2阳性乳腺癌的信号传导机制和治疗策略的疗效。
Zotero 插件
