An overview of molecular targeting of glioblastoma

Glioblastoma (GB) is the most aggressive tumor of the central nervous system (CNS) in adults. In addition to molecular aberrations inherent, specific, or frequent to the disease, it shares, in common with other cancers, alterations in the oncogenic process against which drugs have been designed that are leading to important advances in the treatment of other oncologic diseases. CNS tumors present difficulties in the design of clinical trials, in the evaluation of the response to treatment and its value in determining real effects on survival. The brain is protected by the blood-brain barrier and the barrier adjacent to the tumor, which avoids the deleterious effects of drugs or harmful substances. This makes it very difficult to deliver therapeutic doses to neoplastic brain cells. Due to all this, there have been no major advances in the treatment of GB and several randomized phase III studies with drugs that were promising in earlier phases failed to achieve an increase in survival. Nevertheless, research is intense and is in line with the speed at which molecular alterations can be inhibited by targeted drugs. In the present chapter, we address the different pathways of interest in GB, which are currently being addressed with targeted pharmacological therapy.