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Brain cancer is one of the most aggressive and difficult-to-treat malignancies. Moreover, in the almost 50 years since the start of the war on cancer, the prospects for people who develop brain cancer have improved much more slowly than those of individuals with other types of cancer. Despite a lack of progress in the clinic, research on this group of conditions is advancing steadily, and treatments with the potential to transform the field are on the horizon.
This Nature Outlook is editorially independent. It is produced with third party financial support. About this content.
This Nature Outlook is editorially independent, produced with financial support from a third party.
About
this content.
Research on the blood–brain barrier (BBB) has led to the concept of a complex, dynamic interface between the central nervous system (CNS) and periphery. Banks considers how this new understanding can combine with classical concepts to inform CNS drug delivery strategies and promote BBB integrity in various diseases.
This Opinion argues for a new look at the role of ABC transporters in cancer multidrug resistance to push forward their clinical application as biomarkers and as targets in combination therapies in order to improve anticancer drug efficiency.
Here the authors present a human pluripotent stem cell-derived three-dimensional organoid culture system that is able to recapitulate several aspects of human brain development in addition to modelling the brain disorder microcephaly, which has been difficult to achieve using mouse models.
Glioblastoma is a disease associated with a dismal patient prognosis, necessitating the development of novel therapies. Substantial research effort is being devoted to the development of immunotherapies for glioblastoma. Herein, the rationale and promise for this approach are discussed, together with the challenges and how they might be overcome.
Surgery remains the mainstay of treatment for patients with gliomas, independent of tumour grade, and maximal resection of the tumour is essential for long-term disease control. Herein, the authors discuss the current evidence on associations between the extent of glioma resection and clinical outcomes. They also describe the state-of-the-art surgical oncology approaches aimed at maximizing the extent of tumour resection while minimizing patient morbidity.
Few therapeutic options are currently available for patients with glioblastoma, which are associated with a poor prognosis. Therapies with monoclonal antibodies, alone or linked to cytotoxic payloads, are currently being explored in these patients. Herein, the authors summarize therapeutic strategies based on antibody–drug conjugates (ADCs), targeted against EGFR, and discuss key aspects such as the blood–brain barrier, resistance mechanisms, and the development of specific biomarkers.
In 2016, a revised WHO classification of glioma was published, in which molecular data and traditional histological information are incorporated into integrated diagnoses. Herein, the authors highlight the developments in our understanding of the molecular genetics of gliomas that underlie this classification, and review the current landscape of molecular biomarkers used in the classification of disease subtypes. In addition, they discuss how these advances can promote the development of novel pathogenesis-based therapeutic approaches, paving the way to precision medicine.
Many of the molecular pathways that are aberrant in brain tumours result in reprogramming of metabolism, which creates opportunities forin vivometabolic imaging to improve diagnosis, patient stratification, and disease monitoring. Herein, the molecular basis and strategies for non-invasive metabolic imaging of brain tumours are reviewed.
Lethal pediatric tumors bearing a particular histone H3 mutation upregulate the disialoganglioside GD2, thereby making these tumors susceptible to chimeric antigen receptor T cell–based immunotherapy.
An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer.
The results of in vitro and in vivo screens to identify genes that are essential for the survival of a type of brain cancer show almost no overlap, underlining the need for caution when interpreting in vitro studies. See Letter p355.
Microenvironmental pressures in glioblastoma select for glioma stem cells (GSCs) subpopulations that are maintained through preferential activation of BMI1 and EZH2 in different niches. Given the high degree of intratumor heterogeneity, combined pharmacological inhibition of Polycomb repressive complexes targets proneural and mesenchynmal GSCs and expands lifespan in mice, warranting the therapeutic evaluation of this approach in patients with glioblastoma.
Brain tumours encompass a heterogeneous collection of neoplasms, traditionally classified by histopathological criteria. In 2016, the WHO published an updated classification that, for the first time, defines brain tumour types according to integrated histological and molecular parameters. Furthermore, clinical trial results were reported that inform therapeutic decision-making in diffuse gliomas.
Glioblastoma can be classified based on IDH and TERT promoter mutations, but ~20% of glioblastoma do not have these mutations (TERTpWT-IDHWT glioblastoma). Here, the authors present a genetic landscape of TERTpWT-IDHWT glioblastoma, identifying a telomerase-positive subgroup driven by TERT-structural rearrangements and an ALT-positive subgroup with mutations in ATRX or SMARCAL1.