Overview of a selection of clinical trials targeting the mTOR-pathway in brain tumor patients.

Some study protocols point on the issue of using tissue biomarkers for additional evaluation of treatment-response as follows:1Exploration of associations with pS6 positivity and outcome is planned2Correlation of phosphorylated PKB/Akt and PTEN expression with response is planned3Correlation of tumor objective response rate to established immunohistochemical biomarkers of mTOR pathway activation, including pS6, p4EBP1, pPRAS40, pp70S6K and PTEN is planned4Use of Biomarkers: Phosphatase and tensin homolog (PTEN) and Epidermal Growth Factor Receptor (EGFR)5 Comparison of clinical outcome compared to immunohistochemical markers related to the EGFR and PTEN-PI3K-AKT pathways at baseline is planned6 Evaluation of laboratory variables (phospho-Akt, PTEN status, MGMT expression and promoter methylation status)7Correlation of the activity of the treatment regimen with expression of selected intra-tumoral biomarkers(AZD8055: ATP-competitive mammalian target of rapamycin kinase inhibitor)Overview of a selection of clinical trials targeting the mTOR-pathway in brain tumor patients.