Tissue factor as a regulator of receptor tyrosine kinases in glioblastoma

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, and is one of the most aggressive cancers overall, with very high rates of recurrence and resistance to treatment (1). Those diagnosed with GBM have a rapid onset of disease and progression, with a median survival of only 12 to 15 months from the initial discovery of the tumor (2). Treatment options for GBM tumors are limited, and very little progress has occurred in the discovery of new therapeutic targets for effective treatment. GBM is characterized by over- activation of receptor tyrosine kinases (RTKs)—transmembrane proteins that may promote malignant behaviors, including migration, invasion, proliferation, and tumor-initiating activity (3, 4). GBM cells that exhibit the latter behavior, known as brain tumor initiating cells (BTICs), possess self-renewal capability and contribute to therapy resistance and tumor recurrence (5).