Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology

Simple Summary Despite the remarkable effort of researchers to find more effective treatments for pediatric brain tumors, the prognosis continues to be poor. Forty percent of pediatric patients develop treatment resistance and relapse, and the morbidities and long-term side effects of systemic therapy remain concerning. Significant advances have been made by next-generation genomic profiling. Novel oncogenic drivers have been identified as potential targets for the treatment of pediatric brain tumors. Aptamers, which are synthetic single-strand oligonucleotides, specifically target, bind with high affinity, internalize, and deliver a wide range of therapeutic moieties inside the cells. Although several aptamers have been tested in preclinical and clinical studies for adult glioblastoma, the use of aptamers in pediatric neuro-oncology remains unexplored. Increased knowledge regarding the molecular mechanisms of the pathogenesis of pediatric brain tumors, as well as selection of novel aptamers and/or adaptation of aptamers currently used in adult glioblastoma, might open a novel research field. A relatively new paradigm in cancer therapeutics is the use of cancer cell-specific aptamers, both as therapeutic agents and for targeted delivery of anticancer drugs. After the first therapeutic aptamer was described nearly 25 years ago, and the subsequent first aptamer drug approved, many efforts have been made to translate preclinical research into clinical oncology settings. Studies of aptamer-based technology have unveiled the vast potential of aptamers in therapeutic and diagnostic applications. Among pediatric solid cancers, brain tumors are the leading cause of death. Although a few aptamer-related translational studies have been performed in adult glioblastoma, the use of aptamers in pediatric neuro-oncology remains unexplored. This review will discuss the biology of aptamers, including mechanisms of targeting cell surface proteins, various modifications of aptamer structure to enhance therapeutic efficacy, the current state and challenges of aptamer use in neuro-oncology, and the potential therapeutic role of aptamers in pediatric brain tumors.