Research in Aggressive Brain Tumors: Biology and Precision Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 13461

Special Issue Editor

Department of Neurosurgery, Medical University Vienna, 1090 Vienna, Währinger Gürtel 18-20, Austria;
Comprehensive Cancer Center-Central Nervous System Tumors Unit, Medical University Vienna, 1090 Vienna, Austria
Interests: brain tumor; glioblastoma; ependymoma; targeted therapy; heterogeneity; biomarker; resistance; oncogenic driver

Special Issue Information

Dear Colleagues,

Primary brain tumors affect both children and adults and represent a substantial source of morbidity and mortality worldwide. Among the adult population, glioblastoma is the most common malignant histological type, characterized by a dismal prognosis of less than 2 years, despite multidisciplinary treatment that includes surgical resection and combined radio- chemotherapy. In children, brain tumors including medulloblastoma, gliomas, and ependymomas, rank first among all solid cancers. Survival rates strongly depend on tumor grading and therapeutic options, which are often limited in pediatric patients.

During the last decade, comprehensive genomics and epigenomics studies based on bulk or single-cell omics technologies have elucidated new aspects of molecular alterations and inter-tumor and intra-tumor heterogeneity. These findings improved diagnosis and led to the discovery of new brain tumor subtypes with distinct molecular alterations. Thus, targeted therapies, including MEK and BRAF V600E inhibitors, have been implemented in treatment regimens of pediatric and adult brain tumor patients. However their efficacy is limited due to the presence of multiple genetic abnormalities, limited transport via the blood–brain barrier, intrinsic or acquired resistance mechanisms, or unacceptable side-effects.

This Special Issue will bring the knowledge of genetic, epigenetic, developmental, and microenvironmental heterogeneity into a (pre)clinically relevant context for aggressive pediatric and adult brain tumors

Dr. Daniela Lötsch
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • brain tumor
  • targeted therapy
  • heterogeneity
  • resistance

Published Papers (3 papers)

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Research

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18 pages, 3808 KiB  
Article
Assessing Tumour Haemodynamic Heterogeneity and Response to Choline Kinase Inhibition Using Clustered Dynamic Contrast Enhanced MRI Parameters in Rodent Models of Glioblastoma
by Sourav Bhaduri, Clémentine Lesbats, Jack Sharkey, Claire Louise Kelly, Soham Mukherjee, Arthur Taylor, Edward J. Delikatny, Sungheon G. Kim and Harish Poptani
Cancers 2022, 14(5), 1223; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051223 - 26 Feb 2022
Cited by 3 | Viewed by 1825
Abstract
To investigate the utility of DCE-MRI derived pharmacokinetic parameters in evaluating tumour haemodynamic heterogeneity and treatment response in rodent models of glioblastoma, imaging was performed on intracranial F98 and GL261 glioblastoma bearing rodents. Clustering of the DCE-MRI-based parametric maps (using Tofts, extended Tofts, [...] Read more.
To investigate the utility of DCE-MRI derived pharmacokinetic parameters in evaluating tumour haemodynamic heterogeneity and treatment response in rodent models of glioblastoma, imaging was performed on intracranial F98 and GL261 glioblastoma bearing rodents. Clustering of the DCE-MRI-based parametric maps (using Tofts, extended Tofts, shutter speed, two-compartment, and the second generation shutter speed models) was performed using a hierarchical clustering algorithm, resulting in areas with poor fit (reflecting necrosis), low, medium, and high valued pixels representing parameters Ktrans, ve, Kep, vp, τi and Fp. There was a significant increase in the number of necrotic pixels with increasing tumour volume and a significant correlation between ve and tumour volume suggesting increased extracellular volume in larger tumours. In terms of therapeutic response in F98 rat GBMs, a sustained decrease in permeability and perfusion and a reduced cell density was observed during treatment with JAS239 based on Ktrans, Fp and ve as compared to control animals. No significant differences in these parameters were found for the GL261 tumour, indicating that this model may be less sensitive to JAS239 treatment regarding changes in vascular parameters. This study demonstrates that region-based clustered pharmacokinetic parameters derived from DCE-MRI may be useful in assessing tumour haemodynamic heterogeneity with the potential for assessing therapeutic response. Full article
(This article belongs to the Special Issue Research in Aggressive Brain Tumors: Biology and Precision Therapy)
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19 pages, 3430 KiB  
Article
Machine Learning-Based Analysis of Glioma Grades Reveals Co-Enrichment
by Mateusz Garbulowski, Karolina Smolinska, Uğur Çabuk, Sara A. Yones, Ludovica Celli, Esma Nur Yaz, Fredrik Barrenäs, Klev Diamanti, Claes Wadelius and Jan Komorowski
Cancers 2022, 14(4), 1014; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14041014 - 17 Feb 2022
Cited by 2 | Viewed by 3211
Abstract
Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should [...] Read more.
Gliomas develop and grow in the brain and central nervous system. Examining glioma grading processes is valuable for improving therapeutic challenges. One of the most extensive repositories storing transcriptomics data for gliomas is The Cancer Genome Atlas (TCGA). However, such big cohorts should be processed with caution and evaluated thoroughly as they can contain batch and other effects. Furthermore, biological mechanisms of cancer contain interactions among biomarkers. Thus, we applied an interpretable machine learning approach to discover such relationships. This type of transparent learning provides not only good predictability, but also reveals co-predictive mechanisms among features. In this study, we corrected the strong and confounded batch effect in the TCGA glioma data. We further used the corrected datasets to perform comprehensive machine learning analysis applied on single-sample gene set enrichment scores using collections from the Molecular Signature Database. Furthermore, using rule-based classifiers, we displayed networks of co-enrichment related to glioma grades. Moreover, we validated our results using the external glioma cohorts. We believe that utilizing corrected glioma cohorts from TCGA may improve the application and validation of any future studies. Finally, the co-enrichment and survival analysis provided detailed explanations for glioma progression and consequently, it should support the targeted treatment. Full article
(This article belongs to the Special Issue Research in Aggressive Brain Tumors: Biology and Precision Therapy)
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Review

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24 pages, 1884 KiB  
Review
Tumor Cell Infiltration into the Brain in Glioblastoma: From Mechanisms to Clinical Perspectives
by Fidan Seker-Polat, Nareg Pinarbasi Degirmenci, Ihsan Solaroglu and Tugba Bagci-Onder
Cancers 2022, 14(2), 443; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020443 - 17 Jan 2022
Cited by 44 | Viewed by 7606
Abstract
Glioblastoma is the most common and malignant primary brain tumor, defined by its highly aggressive nature. Despite the advances in diagnostic and surgical techniques, and the development of novel therapies in the last decade, the prognosis for glioblastoma is still extremely poor. One [...] Read more.
Glioblastoma is the most common and malignant primary brain tumor, defined by its highly aggressive nature. Despite the advances in diagnostic and surgical techniques, and the development of novel therapies in the last decade, the prognosis for glioblastoma is still extremely poor. One major factor for the failure of existing therapeutic approaches is the highly invasive nature of glioblastomas. The extreme infiltrating capacity of tumor cells into the brain parenchyma makes complete surgical removal difficult; glioblastomas almost inevitably recur in a more therapy-resistant state, sometimes at distant sites in the brain. Therefore, there are major efforts to understand the molecular mechanisms underpinning glioblastoma invasion; however, there is no approved therapy directed against the invasive phenotype as of now. Here, we review the major molecular mechanisms of glioblastoma cell invasion, including the routes followed by glioblastoma cells, the interaction of tumor cells within the brain environment and the extracellular matrix components, and the roles of tumor cell adhesion and extracellular matrix remodeling. We also include a perspective of high-throughput approaches utilized to discover novel players for invasion and clinical targeting of invasive glioblastoma cells. Full article
(This article belongs to the Special Issue Research in Aggressive Brain Tumors: Biology and Precision Therapy)
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