In silico characterization of missense mutations in PI3K/AKT/mTOR signaling genes in breast cancer and their role in therapeutic resistance

Abstract

Aim: This study aimed to investigate the most frequent missense mutations in key genes of the PI3K/AKT/mTOR signaling pathway to evaluate their potential role in the progression of breast cancer and the development of therapy resistance using computational analyses.

Materials and Methods: Nine genes involved in the PI3K/AKT/mTOR pathway were systematically analyzed by screening mutation databases and applying a range of computational prediction tools to assess the possible deleterious effects of missense variants on protein function and pathway regulation.

Results: Several mutations with predicted deleterious effects were identified, including PTEN (D92H, D92N, R130G, R130Q, C136R, and C136Y), AKT1 (L52R), and AKT2 (R170W). These variants were predicted to contribute to aberrant PI3K/AKT/mTOR pathway activation, enhanced cancer cell survival, and therapeutic resistance in breast cancer.

Conclusion: The findings provided insights into the mutational landscape of breast cancer, proposing potential biomarkers for risk stratification and novel therapeutic targets. Further experimental validation and functional studies are recommended to clarify the clinical significance of these mutations and to guide the development of personalized interventions for breast cancer.