Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration.

Emerging studies have focused on inhibiting AKT activation; here Mehta et al. demonstrate that in primary glioblastoma (Glioblastoma) tumor samples, full-dose inhibition of AKT activity leads to differential responses among samples in the context of cell death and self- renewal, reinforcing the notion that Glioblastoma is a heterogeneous disease. In contrast, low-dose AKT inhibition when combined with fractionation of radiation doses leads to a significant apoptosis-mediated cell death of primary patient-derived Glioblastoma cells. Therefore, low-dose targeted therapies might be better for radiosensitization of primary Glioblastoma cells and further allow for reducing the clinical toxicities often associated with targeting the AKT/PI3K/mTOR pathway. This work emphasizes the discrepancies between cell lines and primary tumors in drug testing, and indicates that there are salient differences between patients, highlighting the need for personalized medicine in treating high-grade glioma 1).

Current standard treatment for glioma patients is surgical removal followed by radiotherapy and adjuvant chemotherapy. Due to therapeutic resistance and tumor recurrence, efforts are ongoing to identify the molecules that are fundamental to regulate the tumor progression and provide additional methods for individual treatment of glioma patients. By studying the initiation and maintenance of glioma, studies focused on the targets of tyrosine kinase receptors including EGFR, PDGFR and other crucial signal pathways such as PI3K/AKT and RAS/RAF/MAPK pathway. Furthermore, recent advances in targeting immunotherapy and stem cell therapy also brought numerous strategies to glioma treatment 2).

Mehta M, Khan A, Danish S, Haffty BG, Sabaawy HE. Radiosensitization of Primary Human Glioblastoma Stem-like Cells With Low-dose AKT Inhibition. Mol Cancer Ther. 2015 Feb 18. pii: molcanther.0708.2014. [Epub ahead of print] PubMed PMID: 25695954.
Lin L, Cai J, Jiang C. Recent advances in targeted therapy for glioma. Curr Med Chem. 2016 Dec 23. [Epub ahead of print] PubMed PMID: 28019637.
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