The Role of RNA and DNA Aptamers in Glioblastoma Diagnosis and Therapy: A Systematic Review of the Literature

Abstract

Glioblastoma (GBM) is the most lethal primary brain tumor of the central nervous system in adults. Despite advances in surgical and medical neuro-oncology, the median survival is about 15 months. For this reason, initial diagnosis, prognosis, and targeted therapy of GBM represent very attractive areas of study. Aptamers are short three-dimensional structures of single-stranded nucleic acids (RNA or DNA), identified by an in vitro process, named systematic evolution of ligands by exponential enrichment (SELEX), starting from a partially random oligonucleotide library. They bind to a molecular target with high affinity and specificity and can be easily modified to optimize binding affinity and selectivity. Thanks to their properties (low immunogenicity and toxicity, long stability, and low production variability), a large number of aptamers have been selected against GBM biomarkers and provide specific imaging agents and therapeutics to improve the diagnosis and treatment of GBM. However, the use of aptamers in GBM diagnosis and treatment still represents an underdeveloped topic, mainly due to limited literature in the research world. On these bases, we performed a systematic review aimed at summarizing current knowledge on the new promising DNA and RNA aptamer-based molecules for GBM diagnosis and treatment. Thirty-eight studies from 2000 were included and investigated. Seventeen involved the use of aptamers for GBM diagnosis and 21 for GBM therapy. Our findings showed that a number of DNA and RNA aptamers are promising diagnostic and therapeutic tools for GBM management.

Molecular Mechanisms of Drug Resistance in Glioblastoma

“…By generation of ROS in the glioma cell line U-87 M, salinomycin caused endoplasmic reticulum stressmediated autophagy and apoptosis [116]. The exercise-induced myokine irisine suppressed tumor proliferation, invasion, and growth of GBM cells by G 2 /M cell [3] cycle arrest and by increasing the levels of p21 [117]. It was shown that sulforaphane (SFN), which is obtained from cruciferous vegetables, induced apoptosis in tumor tissues.…”

“…The induction of cell apoptosis by this SFN-Cys involves the long-term activation of ERK1/2-and ERK1/2-mediated signaling pathways such as the activation of caspase 3 and proteins associated with apoptosis. Macromolecules such as DNA-or RNA-aptamers [3,119], antibodies [120], metal core nanoparticles (NPs), peptide nanoparticles [121][122][123], liposomes (ImmuLipCP) [124], CAR T cells [125], and CRISPR/Cas tools [126] are gradually included in a number of therapeutic drugs or theranostics for glioblastoma in in vivo or in vitro experiments.…”

“…Methods for diagnosing glioblastoma include both neurological examination and imaging tests (magnetic resonance imaging, positron emission tomography, computerized tomography) [3]. Often, it is necessary to carry out a differential diagnosis of GBM from intracranial mass lesions; here, collection and analysis of tumor tissue via brain biopsy or surgical resection can come to the rescue.…”

Insight Into the Prospects for RNAi Therapy of Cancer

“…and have boosted the resurgence of RNAi technology ( Bobbin and Rossi, 2016 ). In the 2016 World Health Organization’s classification of tumors of the central nervous system, glioblastoma (GBM) was categorised as grade IV astrocytoma, which is a commonly seen lethal brain tumor, and many aptamers have already been tested as therapeutic agents in GBM ( Watts and Corey, 2012 ; Louis et al, 2016 ; Nuzzo et al, 2020 ).…”

Predicting Survival in Glioblastoma Patients Using Diffusion MR Imaging Metrics—A Systematic Review

“…Given the urgent need for finding the optimal and targeted treatment option for GBM patients [29,30], and given the proven power of diffusion MRI techniques for applications such as preoperative grading, postoperative assessment of glial tumours and differentiation of GBM from other tumours types (such as brain metastasis or PCNSL [31][32][33]), several studied investigated the association of diffusion MRI metrics with survival outcomes in patients with GBM. Some of these were performed on newly diagnosed GBM patients, while others on recurrent GBM patients.…”