All cancers, including brain tumors, arise from driver genomic and epigenomic alterations and evolve through the sequential acquisition of additional abnormalities. The emergence of next-generation sequencing technologies in the early 2000s enabled rapid and large-scale genomic and epigenomic analyses, leading to substantial advances in our understanding of the molecular pathogenesis of brain tumors. Consequently, driver alterations with potential therapeutic relevance have been progressively identified. Furthermore, continued technological innovations in sequencing technologies have consistently expanded our insights into brain tumor biology. In this review, we summarize recent findings from omics studies on brain tumors and discuss their biological and clinical implications.
Understanding cerebral hemodynamics and metabolism is essential for the diagnosis and treatment of ischemic cerebrovascular disease. Advances in imaging modalities and techniques have enabled the quantitative assessment of hemodynamic compromise and facilitated tailored treatment. In acute ischemic stroke, computed tomography/magnetic resonance perfusion imaging supports the identification of salvageable tissue (the penumbra) and contributes to the selection of endovascular thrombectomy (EVT), particularly within the delayed time window. In chronic intracranial atherosclerotic disease (ICAD), quantitative assessments of cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and oxygen extraction fraction (OEF) are useful for evaluating the risk of recurrence. The results of clinical trials for extracranial-intracranial bypass surgery vary due to differences in selection criteria and perioperative risks; therefore, patient selection based on rigorous hemodynamic evaluation is crucial. Repeated hemodynamic assessments are helpful in determining treatment strategies in moyamoya disease, for instance, which is progressive, even in asymptomatic cases. Postoperative cerebral hemodynamics may present with a mixture of hyperperfusion and hypoperfusion. To reduce the risk of postoperative complications, it is key to accurately understand the hemodynamic status. Collectively, the measurement of cerebral hemodynamics and metabolism is crucial for individualized and evidence-based management of ischemic cerebrovascular disease.
Primary central nervous system lymphoma (PCNSL) is a form of aggressive extranodal lymphoma confined to the central nervous system. Outcomes have substantially improved thanks to the introduction of high-dose methotrexate-based induction chemotherapy and consolidation strategies (including autologous stem cell transplantation); however, therapeutic challenges remain, particularly in elderly patients and those with relapsed or refractory disease. Recent genomic studies have indicates that PCNSL is characterized by frequent MYD88 and CD79B mutations, resulting in constitutive activation of the B-cell receptor and NF-κB signaling pathways, concurrent with an immunosuppressive tumor microenvironment. These insights provide a rationale for the development of targeted therapies and immunotherapies. Bruton's tyrosine kinase inhibitors and immunomodulatory drugs have shown promising activity in both relapsed and frontline settings, and are currently being evaluated in combination with maintenance strategies. CD19-directed chimeric antigen receptor T-cell therapy and CD20×CD3 bispecific antibodies have also emerged as potential therapeutic options for relapsed/refractory PCNSL, with encouraging efficacy and manageable toxicity profiles. This review summarizes the molecular pathogenesis of PCNSL, current standard treatments, and recent advances in targeted therapies and immunotherapeutic strategies that could improve treatment outcomes.
Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome characterized by the development of neoplasms in multiple organs. Hemangioblastoma is one of the most common tumors associated with VHL disease. In 2024, the "Clinical Practice Guidelines for VHL Disease" were established in Japan to provide guidance for the diagnosis, treatment, and management of VHL disease. Furthermore, in 2025, the HIF-2αinhibitor belzutifan was approved for insurance coverage in Japan for VHL-associated tumors, including hemangioblastomas. In this article, we first provide an overview of VHL disease and the "Clinical Practice Guidelines for VHL Disease," and then discuss the diagnosis and treatment of hemangioblastomas, including surgery, endovascular therapy, and radiotherapy. Finally, we review the role of the HIF-2αinhibitor belzutifan. In the future, management of VHL disease and hemangioblastomas will likely require not only individual treatment modalities, but also optimal multimodal strategies combining surgery, radiotherapy, and systemic drug therapy.
Craniopharyngiomas are benign sellar and parasellar tumors that present significant clinical challenge because of their close proximity to the optic apparatus, hypothalamus, and pituitary gland. Recent molecular studies have identified distinct driver mutations, namely, CTNNB1 in adamantinomatous craniopharyngiomas and BRAF V600E in papillary craniopharyngiomas, leading to a deeper understanding of tumor biology and treatment strategies. Advances in endoscopic endonasal transsphenoidal surgery have improved surgical safety and expanded the indications for minimally invasive resection, whereas radiotherapy remains an effective option for residual or recurrent disease. Molecular targeted therapy with BRAF and MEK inhibitors has resulted in remarkable tumor shrinkage in papillary craniopharyngiomas harboring the BRAF V600E mutation, and recent clinical studies have established this approach as a promising treatment option. These agents have emerged not only as effective treatment options for recurrent or refractory disease but also as promising options for neoadjuvant treatment and function-preserving management. Future treatment strategies are likely to incorporate molecular subtypes, patient age, and functional outcomes to achieve individualized care. In addition, the development of reliable preoperative molecular diagnostic techniques, including liquid biopsy, may further facilitate the integration of targeted therapies into routine clinical practice.
