Unravelling the Glioblastoma Tumour Microenvironment: Can Aptamer Targeted Delivery Become Successful in Treating Brain Cancers?

SIMPLE SUMMARY: Glioblastoma multiforme is the most lethal form of brain cancer. To improve patient outcomes, more effective treatments should be designed. Therefore, it is important to understand how this cancer continues to survive via interactions with its environment. Here, we evaluate this environment and several treatments that target it. Moreover, the brain is protected with a barrier that limits the entrance of drugs. Therefore, we review a novel class of treatments, known as aptamers, that can cross this barrier and can carry another drug with them. Our ultimate goal is to encourage the development of more aptamers for the treatment of this deadly cancer. ABSTRACT: The key challenges to treating glioblastoma multiforme (GBM) are the heterogeneous and complex nature of the GBM tumour microenvironment (TME) and difficulty of drug delivery across the blood–brain barrier (BBB). The TME is composed of various neuronal and immune cells, as well as non-cellular components, including metabolic products, cellular interactions, and chemical compositions, all of which play a critical role in GBM development and therapeutic resistance. In this review, we aim to unravel the complexity of the GBM TME, evaluate current therapeutics targeting this microenvironment, and lastly identify potential targets and therapeutic delivery vehicles for the treatment of GBM. Specifically, we explore the potential of aptamer-targeted delivery as a successful approach to treating brain cancers. Aptamers have emerged as promising therapeutic drug delivery vehicles with the potential to cross the BBB and deliver payloads to GBM and brain metastases. By targeting specific ligands within the TME, aptamers could potentially improve treatment outcomes and overcome the challenges associated with larger therapies such as antibodies.