Understanding signal transduction pathways to overcome targeted therapy resistance in glioblastoma

Abstract Glioblastoma (GBM) is the most common yet highly malignant brain tumor. Several surgical techniques and adjuvant therapies have made progressive advances in the treatment of GBM over the past few decades; however, the therapeutic outcomes remain poor because only limited tumor can be surgically resected to minimize damage to the surrounding normal brain tissue. Moreover, there is high resistance of the residual tumors against adjuvant chemotherapies. Therefore, the development of novel chemotherapeutic methods that are effective against residual refractory tumors is urgently needed for GBM treatment. To solve this problem, it is crucial to understand the molecular mechanisms underlying the chemoresistance in GBMs. Owing to the recent advances in high-throughput screening techniques for the genetic, epigenetic, and proteomic analyses of clinical GBM samples, many advances have been made to understand the intracellular molecular networks that regulate the chemoresistance of the GBMs. In fact, multiple candidates have been identified as molecular therapeutic targets for GBM chemotherapy. Thus, in this chapter, the recent knowledge about intracellular signaling networks that possibly contribute to the chemoresistance of GBMs is summarized.