PI3K/AKT/mTOR signaling pathway: an important driver and therapeutic target in triple-negative breast cancer.
Huan-Ping ZhangRui-Yuan JiangJia-Yu ZhuKe-Na SunYuan HuangHuan-Huan ZhouYa-Bing ZhengXiao-Jia WangPublished in: Breast cancer (Tokyo, Japan) (2024)
Triple-negative breast cancer (TNBC) is a highly heterogeneous tumor lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. It has higher aggressiveness and metastasis than other subtypes, with limited effective therapeutic strategies, leading to a poor prognosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway is prevalently over-activated in human cancers and contributes to breast cancer (BC) growth, survival, proliferation, and angiogenesis, which could be an interesting therapeutic target. This review summarizes the PI3K/AKT/mTOR signaling pathway activation mechanism in TNBC and discusses the relationship between its activation and various TNBC subtypes. We also report the latest clinical studies on kinase inhibitors related to this pathway for treating TNBC. Our review discusses the issues that need to be addressed in the clinical application of these inhibitors.
Keyphrases
- signaling pathway
- poor prognosis
- estrogen receptor
- endothelial cells
- epidermal growth factor receptor
- pi k akt
- long non coding rna
- protein kinase
- epithelial mesenchymal transition
- tyrosine kinase
- induced apoptosis
- induced pluripotent stem cells
- cell proliferation
- pluripotent stem cells
- advanced non small cell lung cancer
- vascular endothelial growth factor
- young adults
- oxidative stress
- endoplasmic reticulum