The PI3K/Akt signaling pathway plays a crucial role in regulating ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. This pathway is frequently dysregulated in various cancers, contributing to tumor progression, resistance to therapy, and altered cellular metabolism. Ferroptosis is influenced by multiple pathways, including amino acid, iron, and lipid metabolism, with key regulators such as NRF2, GPX4, SLC7A11, and iron homeostasis playing central roles. The PI3K/Akt pathway interacts with these regulators, modulating their activity and influencing the balance between cell survival and ferroptotic cell death. For instance, the PI3K/Akt pathway can suppress ferroptosis by enhancing NRF2 and GPX4 activity, which protect cells from oxidative stress and lipid peroxidation. Conversely, inhibition of the PI3K/Akt pathway can sensitize cancer cells to ferroptosis, offering a promising therapeutic strategy to overcome drug resistance. The regulation of ferroptosis by the PI3K/Akt pathway involves complex molecular interactions, including the modulation of key enzymes such as GPX4, SLC7A11, and iron transporters. Understanding these interactions provides insights into the molecular mechanisms underlying ferroptosis in cancer and highlights potential therapeutic targets for improving cancer treatment outcomes. The PI3K/Akt pathway's influence on ferroptosis is further supported by studies showing its role in modulating the expression of genes involved in lipid metabolism, redox balance, and cell survival. These findings underscore the importance of targeting the PI3K/Akt pathway to enhance ferroptosis and improve cancer therapy.The PI3K/Akt signaling pathway plays a crucial role in regulating ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. This pathway is frequently dysregulated in various cancers, contributing to tumor progression, resistance to therapy, and altered cellular metabolism. Ferroptosis is influenced by multiple pathways, including amino acid, iron, and lipid metabolism, with key regulators such as NRF2, GPX4, SLC7A11, and iron homeostasis playing central roles. The PI3K/Akt pathway interacts with these regulators, modulating their activity and influencing the balance between cell survival and ferroptotic cell death. For instance, the PI3K/Akt pathway can suppress ferroptosis by enhancing NRF2 and GPX4 activity, which protect cells from oxidative stress and lipid peroxidation. Conversely, inhibition of the PI3K/Akt pathway can sensitize cancer cells to ferroptosis, offering a promising therapeutic strategy to overcome drug resistance. The regulation of ferroptosis by the PI3K/Akt pathway involves complex molecular interactions, including the modulation of key enzymes such as GPX4, SLC7A11, and iron transporters. Understanding these interactions provides insights into the molecular mechanisms underlying ferroptosis in cancer and highlights potential therapeutic targets for improving cancer treatment outcomes. The PI3K/Akt pathway's influence on ferroptosis is further supported by studies showing its role in modulating the expression of genes involved in lipid metabolism, redox balance, and cell survival. These findings underscore the importance of targeting the PI3K/Akt pathway to enhance ferroptosis and improve cancer therapy.