Updated project metadata. Despite currently available treatment, the prognosis of patients with glioblastoma (GBM) is poor and recurrence is inevitable. Several new systemic treatment strategies have been evaluated in the past two decades, but most of those revealed disappointing results. Especially, newly developed tyrosine kinase inhbitors (TKIs) have been studied extensively. These agents inhibit intracellular signaling, i.e. tyrosine kinases, that exert a variety of biological activities, including cell proliferation and migration, and play an important role in GBM. Clinical trials evaluating TKIs have been evaluated for recurrent GBM resulted in minimal improvement in progression-free survival and no overall survival benefit, despite clinical significant benefit in other malignancies such as renal cell cancer. Whether these disappointing results are due to a restricted drug delivery of TKIs through the blood-brain barrier, or due to differential biological characteristics of GBM compared to other malignancies is unknown. MS-based phosphoproteomics was used as an approach for molecular tumor profiling to obtain insight into aberrantly activated signaling pathways and potential drug targets. The objective was to test the feasibility of determining the (phospho)proteomic profiles and kinase activity profiles in tumor tissue by mass spectrometry (MS) after treatment for 10 to 14 days. These profiles were compared to tumor tissue of a control group of patients with newly-diagnosed GBM, who were treated with a resection only.