Advanced Bioinformatics Analysis and Genetic Technologies for Targeting Autophagy in Glioblastoma Multiforme

Abstract

As the most malignant primary brain tumor in adults, a diagnosis of glioblastoma multiforme (GBM) continues to carry a poor prognosis. GBM is characterized by cytoprotective homeostatic processes such as the activation of autophagy, capability to confer therapeutic resistance, evasion of apoptosis, and survival strategy even in the hypoxic and nutrient-deprived tumor microenvironment. The current gold standard of therapy, which involves radiotherapy and concomitant and adjuvant chemotherapy with temozolomide (TMZ), has been a game-changer for patients with GBM, relatively improving both overall survival (OS) and progression-free survival (PFS); however, TMZ is now well-known to upregulate undesirable cytoprotective autophagy, limiting its therapeutic efficacy for induction of apoptosis in GBM cells. The identification of targets utilizing bioinformatics-driven approaches, advancement of modern molecular biology technologies such as clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein (Cas9) or CRISPR-Cas9 genome editing, and usage of microRNA (miRNA)-mediated regulation of gene expression led to the selection of many novel targets for new therapeutic development and the creation of promising combination therapies. This review explores the current state of advanced bioinformatics analysis and genetic technologies and their utilization for synergistic combination with TMZ in the context of inhibition of autophagy for controlling the growth of GBM.

Epigenetic remodeling to improve the efficacy of immunotherapy in human glioblastoma: pre-clinical evidence for development of new immunotherapy approaches

“…Specifically, among the DHA upregulated genes, we found ZBTB6 that significantly suppressed migration, invasion, and proliferation in GBM [47,48], as well as DAXX involved in the suppression of tumor growth and increase of GBM patients' survival [49]. Similarly, DHA down-regulated genes potentially associated to a low OS rate and poor prognosis in GBM such as ERLIN2 and TMEM41B that can inhibit cancer cell growth and metastasis [50,51]. Overall, data obtained indicate that guadecitabine treatment might have a significant role in modulating the profile of GBM cells, increasing their potential sensitivity to immunotherapy.…”

Designing Gold Nanoparticles for Precise Glioma Treatment: Challenges and Alternatives

“…Tumors can be unifocal and multifocal, and can mimic various non-cancerous lesions in the brain such as brain abscess, stroke or multiple sclerosis (MS). The diagnosis of gliomas has been hindered by various obstacles, including tumor heterogeneity, the BBB, and tumor complexity [ 17 , 128 , 130 ].…”

New insights into targeted therapy of glioblastoma using smart nanoparticles

“…The limitations of the effectiveness of existing therapies for GBM and the existence of mechanisms that contribute to therapeutic resistance emphasize the necessity for the creation of innovative diagnostic strategies [ 41 ]. Considering the constraints of current diagnostics and therapeutics, there is a significant need for developing novel diagnostics and therapeutics for glioblastoma.…”

“…Leveraging public genomic databases like TCGA, REMBRANDT, Gravendeel, KEGG, and CGGA, researchers have sought to identify therapeutic targets and construct predictive nomograms [ 49 ]. Ongoing investigations aim to discover novel biomarkers for identifying molecular pathways [ 50 ], employ advanced genome editing technologies such as CRISPR-Cas or CRISPR-Cas9 to overcome chemotherapeutic resistance, utilize targeted miRNAs to silence genes promoting autophagy, and explore the use of plant-derived bioflavonoids to inhibit autophagy and enhance the therapeutic efficacy of TMZ in GBM [ 41 ].…”