Featured
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Research Highlight |
Tovorafenib effective against low-grade gliomas harbouring BRAF fusions
- Peter Sidaway
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Research Highlight |
Dabrafenib–trametinib is effective in paediatric high-grade glioma
- Diana Romero
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Research Highlight |
BRAF plus MEK inhibition effective in papillary craniopharyngioma
- Peter Sidaway
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News & Views |
A new era for glioma therapy — targeting mutant IDH
Hotspot point mutations in IDH1 occur in the vast majority of adult grade 2–3 gliomas. The understanding of their role in tumour biology continues to evolve. Therapeutic targeting of mutant IDH1 with vorasidenib demonstrated highly encouraging efficacy and minimal toxicity in a recent, randomized phase III trial involving patients with low-grade gliomas.
- David A. Reardon
- & Daniel P. Cahill
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Review Article |
Understanding the activity of antibody–drug conjugates in primary and secondary brain tumours
Antibody–drug conjugates (ADCs) have demonstrated efficacy in patients with various cancers, although their antitumour activity in the central nervous system (CNS) might be limited by the blood–brain barrier. In this Review, the authors describe the available clinical data emphasizing the heterogeneous activity of ADCs against primary or secondary brain tumours and ongoing clinical trials in this area. In addition, they discuss physical, biological and molecular determinants of the CNS activity of ADCs, as well as potential strategies to improve delivery of these agents to brain tumours.
- Maximilian J. Mair
- , Rupert Bartsch
- & Matthias Preusser
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Perspective |
Leveraging extrachromosomal DNA to fine-tune trials of targeted therapy for glioblastoma: opportunities and challenges
Glioblastoma, the most common form of brain cancer in adults, has a dismal prognosis and has proven recalcitrant to novel targeted therapies and immunotherapies. Extrachromosomal DNAs (ecDNAs) harbouring oncogenes are increasingly recognized as important drivers of tumour development, evolution and resistance to treatment, particularly in patients with glioblastoma. In this Perspective, the authors summarize key reasons for the failed clinical translation of new therapies for glioblastoma, highlighting the important contributions of ecDNAs. They then focus on the opportunities and challenges of utilizing ecDNAs to improve the likelihood of success in the development of precision medicines for this disease.
- Imran Noorani
- , Paul S. Mischel
- & Charles Swanton
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News & Views |
Cerebrospinal fluid liquid biopsies for medulloblastoma
Cerebrospinal fluid liquid biopsies can enable the characterization and monitoring of medulloblastoma. The analysis of copy-number variations in circulating tumour DNA present in these samples can be used as a biomarker to determine the presence of measurable residual disease, and facilitate the optimal treatment and clinical management of patients with medulloblastoma.
- Joan Seoane
- & Laura Escudero
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Review Article |
The blood–tumour barrier in cancer biology and therapy
The blood–brain barrier regulates the movement of various substances between the blood and the brain and therefore has a crucial role in ensuring normal brain function. In both primary brain tumours and brain metastases, the blood–brain barrier is modified to the blood–tumour barrier (BTB), resulting in altered permeability; however, the BTB continues to restrict the penetration of many therapeutic agents into intracranial tumours. Here, Patricia Steeg describes the current knowledge of BTB structure and function and discusses how this knowledge can be translated into improvements in cancer therapy and patient outcomes.
- Patricia S. Steeg
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Perspective |
The immune landscape of common CNS malignancies: implications for immunotherapy
Patients with primary central nervous system (CNS) malignancies largely do not derive benefit from immune-checkpoint inhibitors. Paradoxically, a subset of those with CNS metastases from tumours located outside of the CNS will respond to the same approach. In this Perspective, the authors explore the key differences in the immune cell composition of primary CNS malignancies and brain metastases and provide guidance on potential alternative immunotherapies that might be effective in patients with these historically difficult-to-treat malignancies.
- Martina Ott
- , Robert M. Prins
- & Amy B. Heimberger
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Evidence-based Guidelines
| Open Access
EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood
Herein, the European Association of Neuro-Oncology (EANO) provides recommendations for the diagnosis, treatment and follow-up of adult patients with diffuse gliomas. These evidence-based guidelines incorporate major changes in diagnostic algorithms based on the 2016 update of the WHO Classification of Tumors of the Central Nervous System as well as on evidence from recent large clinical trials.
- Michael Weller
- , Martin van den Bent
- & Wolfgang Wick
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News & Views |
Methylation extends the reach of liquid biopsy in cancer detection
Measuring the methylation status of cell-free DNA (cfDNA) in plasma holds great potential for the early, noninvasive detection of cancer. Two recent papers published in Nature Medicine showcase the successful application of cfDNA methylation-based cancer detection to two highly challenging scenarios.
- Wenyuan Li
- & Xianghong Jasmine Zhou
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News & Views |
Intraoperative brain tumour identification with deep learning
Developing novel technologies to discriminate malignant tissue from nonmalignant structures and thereby facilitate safe, complete tumour resection is a major priority for advancing oncological neurosurgery. Herein, we discuss a recently reported innovation involving stimulated Raman spectroscopy of intraoperative tissue samples and data interpretation with artificial intelligence, as well as the implications of this approach for neurosurgical oncology.
- Michael L. Martini
- & Eric K. Oermann
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Research Highlight |
Extent of resection is important across glioblastoma molecular subtypes
- David Killock
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Correspondence |
Assembling the brain trust: the multidisciplinary imperative in neuro-oncology
- Ethan B. Ludmir
- , Anita Mahajan
- & Mary Frances McAleer
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Correspondence |
Reply to ‘Assembling the brain trust: the multidisciplinary imperative in neuro-oncology’
- Kenneth Aldape
- , Kevin M. Brindle
- & Richard J. Gilbertson
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News & Views |
Immunotherapy for glioblastoma: quo vadis?
Glioblastoma remains essentially incurable, and new therapeutic approaches are urgently needed. Now, the findings of three serial tissue-based studies suggest that immune-checkpoint inhibition can modify the glioblastoma microenvironment. Following these encouraging observations, the results of two phase III trials of immune-checkpoint inhibition in newly diagnosed glioblastoma, with larger cohorts of patients, are eagerly anticipated.
- Michael Weller
- & Emilie Le Rhun
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Research Highlight |
Lomustine–temozolomide combination efficacious in newly diagnosed glioblastoma
- David Killock
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Consensus Statement
| Open Access
Challenges to curing primary brain tumours
Brain cancer encompasses a diverse range of complex malignancies, many of which are associated with a poor prognosis and require more effective treatments. In this Position Paper, an international panel of clinicians and laboratory-based scientists convened by Cancer Research UK identify and discuss seven challenges that must be overcome if we are to cure all patients with a brain tumour.
- Kenneth Aldape
- , Kevin M. Brindle
- & Richard J. Gilbertson
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News & Views |
Viruses in cancer therapy — from benchwarmers to quarterbacks
A recent clinical trial of a virotherapy approach, consisting of an engineered poliovirus, has provided evidence of apparently durable responses in patients with recurrent glioblastoma. The results of this trial and others indicate that virotherapy might be an effective tool in anticancer immunotherapy. Yet, caution must be exercised until appropriately powered randomized clinical trials truly show efficacy.
- Pierpaolo Peruzzi
- & E. Antonio Chiocca
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Review Article |
Current state of immunotherapy for glioblastoma
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.
- Michael Lim
- , Yuanxuan Xia
- & Michael Weller
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Review Article |
Surgical oncology for gliomas: the state of the art
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.
- Nader Sanai
- & Mitchel S. Berger
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Review Article |
Antibody–drug conjugates in glioblastoma therapy: the right drugs to the right cells
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.
- Hui K. Gan
- , Martin van den Bent
- & Andrew M. Scott
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Research Highlight |
New chemoradiation standard for elderly patients with glioblastoma
- Lisa Hutchinson
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Review Article |
Advances in the molecular genetics of gliomas — implications for classification and therapy
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.
- Guido Reifenberger
- , Hans-Georg Wirsching
- & Michael Weller
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Review Article |
Non-invasive metabolic imaging of brain tumours in the era of 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.
- Michelle M. Kim
- , Abhijit Parolia
- & Sriram Venneti
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Research Highlight |
Chemoradiotherapy for low-grade glioma: battle won, but the war goes on
- David Killock
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Anaplastic glioma: benefit of temozolomide clarified
Medulloblastoma: prognostic subtypes revealed
Low-grade glioma subtypes revealed
CSF DNA provides a snapshot of the glioma genome
Oncolytic viruses prime antitumour immunity
Glioblastoma subtypes revisited
Exploiting mismatch repair in GBM
Astrocytoma cells interconnect to resist radiotherapy