EGFR-Targeted Therapy in Malignant Glioma: Novel Aspects and Mechanisms of Drug Resistance

摘要: Glioblastoma, GBM, is the most frequent brain malignancy in adults. Patients with these tumors survive only, approximately, one year after diagnosis and rarely beyond two years. This poor prognosis is, part, due to our insufficient understanding of complex aggressive nature lack effective therapy. In over-expression EGFR and/or its constitutively activated variant EGFRvIII a major characteristic associated tumorigenesis more phenotypes, such as, invasiveness therapeutic resistance. Consequently, both have been targets for GBM therapy, however, clinical trials EGFR- EGFRvIII-targeted therapies yielded unsatisfactory results molecular basis still unclear. Thus, this review, we will summarize recent advances made EGFR/EGFRvIII pathways key focus on those intrinsic resistance EGFR-targeted For example, emerging evidence indicates an important role that PTEN plays predicting response Aberrant Akt/mTOR pathway has shown contribute resistant phenotype. Also, several studies reported EGFR/EGFRvIII’s cross-talk oncogenic transcription factorSTAT3 receptor tyrosine kinases, (c-Met PDGFR) potentially lead anti-EGFR Other mechanisms, including involving HMG-CoA reductase, also be discussed mini-review. These findings provided new insight into highly interactive generated rationales novel combinational targeted tumors.