Glioblastoma, or glioblastoma multiforme (GBM) is an advanced malignant Grade IV brain tumor. GBM is the most aggressive form of gliomas that develops from astrocytes, which support nerve cells and aids in brain damage repair after injury (Genetic and Rare Diseases Information Center). GBM is multiforme with various deletions, amplifications, and point mutations leading to activation of signal transduction pathways downstream of tyrosine kinase receptors such as epidermal growth factor receptor. EGFR mutations are most commonly observed in GBM with EGFRvIII (exon 2-7 deletion) as the most frequently occurring mutation. EGFR amplification, overexpression and mutation are frequently observed up to 50% in GBM. Current EGFR inhibitors approved in NSCLC have not been proven effective in GBM possible due to limited CNS penetration and/or EGFRvIII resistance.
The standard of care for GBM treatment typically involves surgical resection of the tumor followed by radiotherapy, chemotherapy (temozolomide) with or without alternating electrical field therapy. Even with optimal treatment, GBM is an incurable tumor with a median survival of only 15 months.