Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy

Am J Cancer Res. 2021 Oct 15;11(10):5155-5183. eCollection 2021.ABSTRACTBreast cancer is the most prevalent type of cancer among women. Several types of drugs, targeting the specific proteins expressed on the breast cancer cell surface (such as receptor tyrosine kinases and immune checkpoint regulators) and proteins involved in cell cycle and motility (including cyclin-dependent kinases, DNA stabilisers, and cytoskeleton modulators) are approved for different subtypes of breast cancer. However, breast cancer also has a poor response to conventional chemotherapy due to intrinsic and acquired resistance, and an Akt fingerprint is detectable in most drug-resistant cases. Overactivation of Akt and its upstream and downstream regulators in resistant breast cancer cells is considered a major potential target for novel anti-cancer therapies, suggesting that Akt signalling acts as a cellular mechanism against chemotherapy. The present review has shown that sustained activation of Akt results in resistance to different types of chemotherapy. Akt signalling plays a cellular defence role against chemotherapy and (1) enhances multi-drug resistance, (2) increases reactive oxygen species at breast tumor microenvironment, (3) enhances anaerobic metabolism, (4) inhibits the tricarboxylic cycle, (5) promotes PD-L1 upregulation, (6) inhibits apoptosis, (7) increases glucose uptake, and more importantly (8) recruits and interconnects the plasma membrane, nucleus, endoplasmic reticulum, and mito...
Source: Cell Research - Category: Cytology Authors: Source Type: research