REVIEW article
Front. Aging Neurosci.
Sec. Neuroinflammation and Neuropathy
This article is part of the Research TopicThe Role of Microenvironment in Brain Tumors: Mechanisms, Progression, and Therapeutic StrategiesView all articles
Brain microenvironment orchestrates highly aggressive tumor variants: current trends and therapeutic approaches
Provisionally accepted
- 1Virginia Commonwealth University, Richmond, United States
- 2University of Nebraska Medical Center, Omaha, United States
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Brain tumors exhibit some of the major challenges in the field of oncology owing to their highly heterogeneous, complex, and aggressive nature. The complex anatomy and aggressiveness of the cancer contribute to high mortality and morbidity worldwide. Moreover, the complexity of genetic mutations and dysregulation molecular processes often culminates into treatment resistance. Consequently, brain tumors have become a serious threat to patients' lives and overall health. Although advancements in the treatment strategies have been made, but the current knowledge amounts to a drop in the ocean, and many patients still struggling with the disease and exhibit poor prognosis. Hence, there is an urgent need to rigorously expand and fasten the ongoing research to address this clinical challenge. This review explores the components of the brain microenvironment that influence tumor homing and progression towards the aggressive phenotype, with the special emphasis on how these pathways could be therapeutically targeted. The complex milieu of brain niche is further amplified by the infiltrating immune cells, which reshape the brain connectome through novel interactions with resident brain cells. We also discuss the different targeted chemotherapeutic, immunotherapeutic, and combinatorial strategies to limit brain metastasis, which currently has limited therapeutic options. Therefore, this review will discuss all the aspects of brain tumor microenvironment (TME), current strategies, and futuristic insights. We will be discussing the individual components of the tumor microenvironment like BBB, stem cells, astrocytes, immune cells, and non-cellular components like ECM. Further, we also shed some light on current therapies and future strategies targeting these microenvironment components.
Keywords: tumor, Brain, microenvironment, Mortality, therapy
Received: 15 Jul 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Mishra, Dickinson and Maurya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shailendra Kumar Maurya, shailendramauryak001@gmail.com
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