A review of recent advances in magnetic nanoparticle-based theranostics of glioblastoma

Rapid vascular growth, infiltrative cells and high tumor heterogenicity are some glioblastoma multiforme (GBM) characteristics, making it the most lethal form of brain cancer. Low efficacy of the conventional treatment modalities leads to rampant disease progression and a median survival of 15 months. Magnetic nanoparticles (MNPs), due to their unique physical features/inherent abilities, have emerged as a suitable theranostic platform for targeted GBM treatment. Thus, new strategies are being designed to enhance the efficiency of existing therapeutic techniques such as chemotherapy, radiotherapy, and so on, using MNPs. Herein, the limitations of the current therapeutic strategies, the role of MNPs in mitigating those inadequacies, recent advances in the MNP-based theranostics of GBM and possible future directions are discussed.

Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity

Glioblastoma is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of glioblastoma have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned across glioblastoma’s hallmark histomorphologic niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to distinct histologic patterns across 20 patients and propose diverse molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Moreover, we highlight differential drug sensitivities and relative chemoresistance in glioblastoma cell lines with enhanced KRAS programs. Importantly, these pharmacological differences are less pronounced in transcriptional glioblastoma subgroups suggesting that this model may provide insights for targeting heterogeneity and overcoming therapy resistance.

Radiotherapy for Glioblastoma: Clinical Issues and Nanotechnology Strategies

Glioblastoma (GBM) is the most common primary brain cancer in adults with poor prognosis. Despite the current state of knowledge on its genetic characteristics, relatively little progress has been made...

Unveiling a Ghost Proteome in the Glioblastoma Non-Coding RNAs

Glioblastoma is the most common brain cancer in adults. Nevertheless, the median survival time is 15 months, if treated with at least a near total resection and followed by radiotherapy in association with temozolomide. In glioblastoma (GBM), variations of non-coding ribonucleic acid (ncRNA) expression have been demonstrated in tumor processes, especially in the regulation of major signaling pathways. Moreover, many ncRNAs present in their sequences an Open Reading Frame (ORF) allowing their translations into proteins, so-called alternative proteins (AltProt) and constituting the “ghost proteome.” This neglected world in GBM has been shown to be implicated in protein–protein interaction (PPI) with reference proteins (RefProt) reflecting involvement in signaling pathways linked to cellular mobility and transfer RNA regulation. More recently, clinical studies have revealed that AltProt is also involved in the patient’s survival and bad prognosis. We thus propose to review the ncRNAs involved in GBM and highlight their function in the disease.