Effective treatments for brain tumors remain one of the most urgent and unmet needs in modern oncology. This is due not only to the presence of the neurovascular unit/blood-brain barrier (NVU/BBB) but also to the heterogeneity of barrier alteration in the case of brain tumors, which results in what is referred to as the blood-tumor barrier (BTB). Herein, we discuss this heterogeneity, how it contributes to the failure of novel pharmaceutical treatment strategies, and why a "whole brain" approach to the treatment of brain tumors might be beneficial. We discuss various methods by which these obstacles might be overcome and assess how these strategies are progressing in the clinic. We believe that by approaching brain tumor treatment from this perspective, a new paradigm for drug delivery to brain tumors might be established.
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http://dx.doi.org/10.3390/pharmaceutics12121205 | DOI Listing |
J Nanobiotechnology
January 2025
Department of Pharmacy The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation.
View Article and Find Full Text PDFNeurosurg Rev
January 2025
Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, 113-8655, Japan.
Recent technologic advancements have facilitated the use of hypofractionated Gamma Knife-based radiosurgery (HF-GKRS) to treat large lesions or those in eloquent areas. This study aimed to analyze the preliminary results of HF-GKRS for these meningiomas, and to determine its effectiveness and safety. This single-center retrospective study analyzed data of patients who underwent HF-GKRS for large meningiomas or those in eloquent areas with > 6 months of follow-up.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.
View Article and Find Full Text PDFSci Rep
January 2025
Biochemistry Department, Biotechnology Research Institute, National Research Centre, Dokki, Giza, Egypt.
Glioblastoma multiforme (GBM) is the most prevalent, treatment-resistant, and fatal form of brain malignancy. It is characterized by genetic heterogeneity, and an infiltrative nature, and GBM treatment is highly challenging. Despite multimodal therapies, clinicians lack efficient prognostic and predictive markers.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.
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