Multiple forms of cell death: A focus on the PI3K/AKT pathway

Cell death is a natural biological process that occurs in living organisms. Since 1963, extensive research has shed light on the occurrence, progress, and final outcome of cell death. According to different cell phenotypes, it is classified into different types, including apoptosis, pyroptosis, necroptosis, autophagy, ferroptosis, cuproptosis, and so on. However, regardless of the form of cell death, what we ultimately expect is the disappearance of abnormal cells, such as tumor cells, while normal cells survive. As a result, it is vital to investigate the details of cell death, including death triggers, potent regulators, and executioners. Although significant progress has been made in understanding molecular pathways of cell death, many aspects remain unclear because of the complex regulatory networks in cells. Among them, the phosphoinositide-3-kinase (PI3K)/protein kinase B(AKT) pathway is discovered to be a crucial regulator of the cell death process. AKT, as a proto-oncogene, has become a major focus of attention in the medical community due to its role in regulating a multiplicity of cellular functions counting metabolism, immunity, proliferation, survival, transcription, and protein synthesis. Here, we explored the connection between the PI3K/AKT pathway and cell death, aiming to enhance our comprehension of the mechanism underlying this process. Such knowledge may pave the way for the subsequent development of more effective disease treatments, such as finding suitable targets for drug intervention.