Protein Based Nanoscaffolds Incorporated with Anticancer Drug for Brain Tumor Targeting

Abstract

Glioblastoma is an aggressive and inevitably recurrent primary intra-axial brain tumor with a dismal prognosis. Glioblastoma, a World Health Organization grade IV astrocytoma, with an incidence in North newlineAmerica of 5.0 per 100,000 population, representing 15 to 20% of all primary intracranial neoplasms, in adults, is highly aggressive, with an unusually dismal prognosis (death typically results in the first 15-16 months after diagnosis), with a 5-year survival rate of 5%. These tumors arise from astrocytes and oligodendrocytes. The majority of glioblastoma are found in the supratentorial brain (frontal, temporal, newlineparietal, and occipital lobes), with rare occurrence in the cerebellum, the brain stem and the spinal cord. Glioblastomas may develop in de novo patients as a primary glioblastoma or through progression from newlinelower-grade astrocytomas in as secondary glioblastomas. Glioblastoma were previously classified into 4 subtypes: 1) proneural, 2) neural, 3) classical, and 4) mesenchymal, with the proneural subtype possibly newlineconferring a more favorable prognosis in younger patients. However, recent analysis of transcriptomes of glioma have revealed 3 subtypes strongly enriched with mRNAs associated with classical, proneural and newlinemesenchymal subtypes, but not with the neural subtype, suggesting that this subtype may have arisen from contamination of the original samples with nontumor cells. The highly infiltrative nature of GBM makes newlinecomplete resection at the cellular level nearly impossible. Also, abundant hypoxic regions provide perivascular niches for glioma initiating cells (GICs). These self-renewing cells can yield potentially more newlineaggressive recurrent tumors that are radioresistant and chemoresistant, large intertumor and intratumor heterogeneity have complicated targeted therapy development. Based on their genetic and epigenetic newlinemarkers, GBMs were previously classified by The Cancer Genome Atlas (TCGA) into four clusters: mesenchymal, classical, proneural, and neural.