Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer

Abstract

The global challenge posed by cancer, marked by rising incidence and mortality rates, underscores the urgency for innovative therapeutic approaches. The PI3K/Akt signaling pathway, frequently amplified in various cancers, is central in regulating essential cellular processes. Its dysregulation, often stemming from genetic mutations, significantly contributes to cancer initiation, progression, and resistance to therapy. Concurrently, ferroptosis, a recently discovered form of regulated cell death characterized by iron-dependent processes and lipid reactive oxygen species buildup, holds implications for diseases, including cancer. Exploring the interplay between the dysregulated PI3K/Akt pathway and ferroptosis unveils potential insights into the molecular mechanisms driving or inhibiting ferroptotic processes in cancer cells. Evidence suggests that inhibiting the PI3K/Akt pathway may sensitize cancer cells to ferroptosis induction, offering a promising strategy to overcome drug resistance. This review aims to provide a comprehensive exploration of this interplay, shedding light on the potential for disrupting the PI3K/Akt pathway to enhance ferroptosis as an alternative route for inducing cell death and improving cancer treatment outcomes.

Methylome-wide analysis in systemic microbial-induced experimental periodontal disease in mice with different susceptibility

“…Akt1, identified as a highly connected central node, is particularly significant because of its involvement in multiple cellular signaling pathways. It regulates cell growth, survival, and metabolism, indicating its role as a master regulator within the network ( Yang et al., 2019 ; Su et al., 2024 ). This extensive connectivity underscores the importance of the PI3K/AKT pathway in maintaining cellular homeostasis and responding to external stimuli ( Engelman et al., 2006 ).…”

“…Given these findings, the PI3K/AKT signaling pathway’s focus is justified by its central role in regulating vital cellular processes and maintaining cellular homeostasis. This pathway’s critical functions in cell growth, survival, and metabolism make it a key area of interest for further research and potential therapeutic interventions ( Yang et al., 2019 ; Su et al., 2024 ).…”