Nature Outlook |

Brain cancer

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.

Features and comment

Research on one of the deadliest malignancies is yielding potentially game-changing insights — and treatments.

Outlook | | Nature

Brain cancer comprises only 2% of cancers, but is notoriously difficult to treat. Understanding the location of such tumours, as well as the underlying genetics, will help to tackle this devastating disease.

Outlook | | Nature

A flood of sequencing data is enabling researchers to uncover how tumours differ from each other, and what such variation means for treatment strategies.

Outlook | | Nature

At Novocure, we are very proud of our ongoing commitment and dedication to improving the lives of people with brain cancer. Our patients, their families and caregivers are at the heart of everything we do. They are the people who drive us forward to achieve our goal of delivering a cancer therapy that can extend and maintain the quality of many patients’ lives. We invited one of our many glioblastoma patients to tell us about his own journey from diagnosis to treatment with TTFields. In his own words, the following inspirational story was provided by Brian Biggs of his own experience of living with this devastating disease.

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More from Nature Research

Genetically altered mice are used widely to model human diseases, but as the organization of the human brain is so much more complicated than that of a rodent, brain development diseases have not been tackled. Juergen Knoblich and colleagues have developed an alternative model, a three-dimensional organoid culture system, using human pluripotent stem cells, that recapitulates several aspects of human brain development. The system mimics the temporal development of neuronal subtypes and the organization of the tissue into layers. In proof-of-principle experiments the authors produce a microcephaly model using patient-derived induced pluripotent stem cells and describe defects in neuronal differentiation not previously observed in rodent models.

Article | | Nature

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.

Review Article | | Nature Reviews Clinical Oncology

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.

Review Article | | Nature Reviews Clinical Oncology

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.

Review Article | | Nature Reviews Clinical Oncology

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.

Review Article | | Nature Reviews Clinical Oncology

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.

Review Article | | Nature Reviews Clinical Oncology

Most high-throughput target discovery screens for glioblastoma have been limited to in vitro models with uncertain physiological relevance. Here, Jeremy Rich and colleagues perform two parallel RNA interference screens for transcriptional regulators, comparing an in vitro screen in cell lines to an in vivo screen that recapitulates the tumour microenvironment. They find several transcriptional elongation factors that are specifically required for glioblastoma cell survival in vivo, particularly the transcriptional pause release factor JMJD6 which is highly expressed in gliomas. This type of in vivo functional screen has the potential to uncover novel therapeutic targets for cancer that have not been identified in previous in vitro approaches.

Letter | | Nature

Most high-throughput target discovery screens for glioblastoma have been limited to in vitro models with uncertain physiological relevance. Here, Jeremy Rich and colleagues perform two parallel RNA interference screens for transcriptional regulators, comparing an in vitro screen in cell lines to an in vivo screen that recapitulates the tumour microenvironment. They find several transcriptional elongation factors that are specifically required for glioblastoma cell survival in vivo, particularly the transcriptional pause release factor JMJD6 which is highly expressed in gliomas. This type of in vivo functional screen has the potential to uncover novel therapeutic targets for cancer that have not been identified in previous in vitro approaches.

News & Views | | Nature

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.

Article | | Nature Medicine

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.

Year in Review | | Nature Reviews Neurology

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.

Article | Open Access | | Nature Communications