Biomedicine & Pharmacotherapy (Feb 2023)
Progress in targeting PTEN/PI3K/Akt axis in glioblastoma therapy: Revisiting molecular interactions
Abstract
Glioblastoma (GBM) is one of the most malignant cancers of central nervous system and due to its sensitive location, surgical resection has high risk and therefore, chemotherapy and radiotherapy are utilized for its treatment. However, chemoresistance and radio-resistance are other problems in GBM treatment. Hence, new therapies based on genes are recommended for treatment of GBM. PTEN is a tumor-suppressor operator in cancer that inhibits PI3K/Akt/mTOR axis in diminishing growth, metastasis and drug resistance. In the current review, the function of PTEN/PI3K/Akt axis in GBM progression is evaluated. Mutation or depletion of PTEN leads to increase in GBM progression. Low expression level of PTEN mediates poor prognosis in GBM and by increasing proliferation and invasion, promotes malignancy of tumor cells. Moreover, loss of PTEN signaling can result in therapy resistance in GBM. Activation of PTEN signaling impairs GBM metabolism via glycolysis inhibition. In contrast to PTEN, PI3K/Akt signaling has oncogenic function and during tumor progression, expression level of PI3K/Akt enhances. PI3K/Akt signaling shows positive association with oncogenic pathways and its expression similar to PTEN signaling, is regulated by non-coding RNAs. PTEN upregulation and PI3K/Akt signaling inhibition by anti-cancer agents can be beneficial in interfering GBM progression. This review emphasizes on the signaling networks related to PTEN/PI3K/Akt and provides new insights for targeting this axis in effective GBM treatment.