Advances In Brain Tumor Therapy: Role Of The Tumor Microenvironment In Pharmacological Strategies

Abstract

Glioblastoma and other high-grade gliomas (malignancies) remain among the most clinically recalcitrant cancer subtypes due to rapid response phenotype, the general insensitivity to conventional therapy and complex tumor microenvironment (TME). The mutual interaction between the tumor cell and the surrounding micro-environment synergistically promotes the survival of cancer cells and their invasion, on the one hand, and acts as effective obstacles to the application of pharmacological methods, on the other hand.The current review overviews the recent progress in cancer treatment in the brain including the pharmacological approaches to TME elements. Recent antineoplastic anti-angiogenic drugs, the first immunotherapies with the use of immune checkpoint blockers and CAR-T cell therapy, and the combination of antineoplastic agents with modulations of metabolism, stroma, and TME (extracellular matrix) are evaluated against recently conducted clinical trials and supporting preclinical studies. At the same time, advancements aimed at overcoming the challenges associated with the blood brain barrier such as nanoparticle based and biologic based are touched upon. New modalities of therapy such as nanoparticles, biologics, and gene editors are noted to have the potential of redefining therapeutics.Nonetheless, despite the great achievement that has been achieved, there are major challenges that still exist including tumor and TME heterogeneity, ineffective preclinical models, and adaptive resistance management.The review highlights the significance of incorporating personalized medicine models and combination approaches towards optimizing therapeutic outcomes and reducing unwanted effects.In summary, addressing the brain tumor microenvironment is a worthwhile enchantment that has the prospect of creating a vital enhancement in patient outcomes. Intensified multidisciplinary research and well-conducted clinical trials would be essential in realizing the transformation of the breakthroughs into long-term and practical contributions to value-adding initiatives to the patients with brain tumors.