Brain Tumor: From Pathophysiology to Novel Therapies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 1083

Special Issue Editor


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Guest Editor
Neurosurgery Department, Centro Hospitalar Universitário São João, Alameda Professor Hernâni Monteiro, 4200-319 Oporto, Portugal
Interests: neuro-oncologia; cirurgia de tumores cerebrais com o doente acordado e mapeamento cerebral; cirurgia de tumores cerebrais com imunofluorescência; cirurgia de gliomas de baixo grau; cirurgia da epilepsia; cirurgia intracraniana; patologia da coluna vertebral
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Dear Colleagues,

Brain tumors comprise a heterogeneous group of neoplasms that pose major clinical challenges due to their location, aggressiveness, and limited treatment options. Their pathophysiology involves complex genetic and epigenetic alterations that disrupt normal signaling pathways, leading to uncontrolled cell proliferation, angiogenesis, and invasive growth into surrounding brain tissue. Glioblastoma is characterized by mutations in genes such as EGFR, PTEN, and IDH, as well as profound intratumoral heterogeneity, which contributes to therapeutic resistance and recurrence.

Standard treatment typically combines maximal safe surgical resection, radiotherapy, and temozolomide chemotherapy, but prognosis remains poor, with a median survival of around 15 months.

Population-based research is important and necessary, focused on age-specific incidence, identification of risk factors, and development of biomarkers with clinical applicability. Recent advances aim to overcome these limitations through targeted molecular therapies, immunotherapy, tumor-treating fields, and precision medicine approaches guided by genomic and transcriptomic profiling. Emerging research into the tumor microenvironment and cancer stem cells is opening new avenues for intervention. These innovations bring hope for more effective, personalized treatments, ultimately aiming to improve survival and quality of life for patients with brain tumors.

Prof. Dr. Paulo Linhares
Guest Editor

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Keywords

  • glioblastoma
  • immunotherapy
  • molecular subtype
  • radiotherapy
  • molecular therapy
  • emerging treatment
  • drug resistance
  • MRI
  • immune surveillance
 

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Published Papers (1 paper)

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Review

17 pages, 6344 KB  
Review
From Epigenetic Constraint to Evolutionary Escape: Cell-State Transitions and Selective Pressures During Malignant Transformation in Lower-Grade Gliomas
by Hao Wu, Yi Wei, Xing-Ding Zhang and Lin Qi
Biomedicines 2026, 14(5), 985; https://doi.org/10.3390/biomedicines14050985 - 25 Apr 2026
Viewed by 772
Abstract
Lower-grade gliomas (LGGs) often follow a relatively protracted clinical course; however, a substantial proportion eventually undergo malignant transformation to high-grade, treatment-refractory disease. This process has traditionally been interpreted in the context of stepwise histopathologic progression and recurrent genetic alterations. Increasing evidence, however, suggests [...] Read more.
Lower-grade gliomas (LGGs) often follow a relatively protracted clinical course; however, a substantial proportion eventually undergo malignant transformation to high-grade, treatment-refractory disease. This process has traditionally been interpreted in the context of stepwise histopathologic progression and recurrent genetic alterations. Increasing evidence, however, suggests that malignant transformation is more accurately understood as an evolutionary process shaped by the interplay among epigenetic constraints, cell-state plasticity, and selective pressures. In this review, we examine current evidence supporting a model in which early LGGs, particularly isocitrate dehydrogenase (IDH)-mutant tumors, are initially maintained in relatively restricted cellular states by metabolically imposed epigenetic programs, but progressively escape these constraints under the cumulative influence of therapy, hypoxia, immune remodeling, and genomic instability. We summarize recent advances demonstrating that progression from lower-grade to high-grade disease is accompanied by cell-state transitions characterized by altered lineage identity, acquisition of stem-like features, increased proliferative capacity, and adaptation to cellular stress. We further discuss how these transitions are reinforced by microenvironmental evolution, including vascular remodeling, extracellular matrix reorganization, and changes in immune composition, thereby creating conditions that favor clonal expansion, invasion, and therapeutic resistance. Particular attention is given to longitudinal, single-cell, and spatially resolved studies, which collectively indicate that malignant transformation is not a discrete event but a continuous process of evolutionary selection and phenotypic reprogramming. Finally, we discuss the translational implications of this framework for early risk stratification, biomarker development, and mechanism-based therapeutic intervention. By reframing malignant transformation in LGGs as a process of cell-state escape under persistent selective pressure, this review aims to provide an integrated view of glioma progression and to highlight new opportunities for precision monitoring and treatment. Full article
(This article belongs to the Special Issue Brain Tumor: From Pathophysiology to Novel Therapies)
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