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Radiation Biology of Glioblastoma—Defining Clinically Relevant Novel Targets and New Therapies for Improved Patient Outcomes

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

Deadline for manuscript submissions: closed (1 September 2023) | Viewed by 5984

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Special Issue Editors

Dr. Thomas Flannery

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Guest Editor

Department of Neurosurgery, Royal Victoria Hospital Belfast and Gamma Knife Centre, St. James’s Institute of Clinical Oncology, Leeds LS9 7LP, UK
Interests: glioma biology; surgical resection of gliomas; radiation biology of brain tumors

Prof. Dr. Kevin Prise

E-Mail Website
Co-Guest Editor

Patrick G. Johnston Centre for Cancer Research, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, UK
Interests: radiation biology; low dose radiation risk; radiation quality; cell and tissue signaling mechanisms

Special Issue Information

Dear Colleagues,

Glioblastoma remains one of the most difficult to treat primary malignant brain tumors. Despite the intensive efforts of clinicians and researchers, the outcome of these patients remains poor, not just in terms of survival statistics, but also in terms of disability and emotional distress for patients and their families. As a community, the onus is on us to explore novel more effective therapies to try and improve outcomes for these most unfortunate patients.

Radiotherapy still forms the main component of the post-surgical treatment of glioblastoma patients and although it has been shown to confer improved survival in conjunction with temozolomide (particularly in the MGMT-methylated cohort), the promise of other targeted agents, e.g., bevacizumab, EGRF-based approaches have failed to materialize in the clinical context. With a greater understanding of the mechanisms of radiation resistance employed by tumor cells and their surrounding microenvironment, we can identify novel, clinically effective strategies that can be used to safely optimize the effects of radiation treatment. The incorporation of new radiotherapy approaches, including FLASH and particle beams, offers potential improvements for sparing normal brain tissue if they can be biologically optimized.

This Special Issue of Cancers invites contributions (original research articles, reviews, and other relevant contributions) that highlight our enhanced understanding of the radiation biology of glioblastomas and novel therapeutic strategies that may have significant clinical benefit for our patients.

We look forward to receiving your contributions.

Dr. Thomas Flannery
Prof. Dr. Kevin Prise
Guest Editors

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

radiation
glioblastoma
novel targeted therapies
quality of life
advanced radiotherapies

Published Papers (2 papers)

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Research

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12 pages, 1097 KiB

Open AccessArticle

Apparent Diffusion Coefficient Metrics to Differentiate between Treatment-Related Abnormalities and Tumor Progression in Post-Treatment Glioblastoma Patients: A Retrospective Study

by Rik van den Elshout, Siem D. A. Herings, Manoj Mannil, Anja M. M. Gijtenbeek, Mark ter Laan, Robert J. Smeenk, Frederick J. A. Meijer, Tom W. J. Scheenen and Dylan J. H. A. Henssen

Cancers 2023, 15(20), 4990; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15204990 - 14 Oct 2023

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Abstract

Distinguishing treatment-related abnormalities (TRA) from tumor progression (TP) in glioblastoma patients is a diagnostic imaging challenge due to the identical morphology of conventional MR imaging sequences. Diffusion-weighted imaging (DWI) and its derived images of the apparent diffusion coefficient (ADC) have been suggested as diagnostic tools for this problem. The aim of this study is to determine the diagnostic accuracy of different cut-off values of the ADC to differentiate between TP and TRA. In total, 76 post-treatment glioblastoma patients with new contrast-enhancing lesions were selected. Lesions were segmented using a T1-weighted, contrast-enhanced scan. The mean ADC values of the segmentations were compared between TRA and TP groups. Diagnostic accuracy was compared by use of the area under the curve (AUC) and the derived sensitivity and specificity values from cutoff points. Although ADC values in TP (mean = 1.32 × 10⁻³ mm²/s; SD = 0.31 × 10⁻³ mm²/s) were significantly different compared to TRA (mean = 1.53 × 10⁻³ mm²/s; SD = 0.28 × 10⁻³ mm²/s) (p = 0.003), considerable overlap in their distributions exists. The AUC of ADC values to distinguish TP from TRA was 0.71, with a sensitivity and specificity of 65% and 70%, respectively, at an ADC value of 1.47 × 10⁻³ mm²/s. These findings therefore indicate that ADC maps should not be used in discerning between TP and TRA at a certain timepoint without information on temporal evolution. Full article

(This article belongs to the Special Issue Radiation Biology of Glioblastoma—Defining Clinically Relevant Novel Targets and New Therapies for Improved Patient Outcomes)

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Review

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32 pages, 2690 KiB

Open AccessReview

Perspective on the Use of DNA Repair Inhibitors as a Tool for Imaging and Radionuclide Therapy of Glioblastoma

by Liesbeth Everix, Shankari Nair, Cathryn H. S. Driver, Ingeborg Goethals, Mike M. Sathekge, Thomas Ebenhan, Charlot Vandevoorde and Julie Bolcaen

Cancers 2022, 14(7), 1821; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071821 - 03 Apr 2022

Cited by 3 | Viewed by 4294

Abstract

Despite numerous innovative treatment strategies, the treatment of glioblastoma (GB) remains challenging. With the current state-of-the-art therapy, most GB patients succumb after about a year. In the evolution of personalized medicine, targeted radionuclide therapy (TRT) is gaining momentum, for example, to stratify patients based on specific biomarkers. One of these biomarkers is deficiencies in DNA damage repair (DDR), which give rise to genomic instability and cancer initiation. However, these deficiencies also provide targets to specifically kill cancer cells following the synthetic lethality principle. This led to the increased interest in targeted drugs that inhibit essential DDR kinases (DDRi), of which multiple are undergoing clinical validation. In this review, the current status of DDRi for the treatment of GB is given for selected targets: ATM/ATR, CHK1/2, DNA-PK, and PARP. Furthermore, this review provides a perspective on the use of radiopharmaceuticals targeting these DDR kinases to (1) evaluate the DNA repair phenotype of GB before treatment decisions are made and (2) induce DNA damage via TRT. Finally, by applying in-house selection criteria and analyzing the structural characteristics of the DDRi, four drugs with the potential to become new therapeutic GB radiopharmaceuticals are suggested. Full article

(This article belongs to the Special Issue Radiation Biology of Glioblastoma—Defining Clinically Relevant Novel Targets and New Therapies for Improved Patient Outcomes)

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