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Review
. 2020 Sep 3;12(9):2511.
doi: 10.3390/cancers12092511.

Radioresistance in Glioblastoma and the Development of Radiosensitizers

Md Yousuf Ali  1   2   3 , Claudia R Oliva  2   3 , Abu Shadat M Noman  4   5 , Bryan G Allen  2   3 , Prabhat C Goswami  2   3 , Yousef Zakharia  6 , Varun Monga  6 , Douglas R Spitz  2   3 , John M Buatti  3 , Corinne E Griguer  2   3
Affiliations
Review

Radioresistance in Glioblastoma and the Development of Radiosensitizers

Md Yousuf Ali et al. Cancers (Basel). .

Abstract

Ionizing radiation is a common and effective therapeutic option for the treatment of glioblastoma (GBM). Unfortunately, some GBMs are relatively radioresistant and patients have worse outcomes after radiation treatment. The mechanisms underlying intrinsic radioresistance in GBM has been rigorously investigated over the past several years, but the complex interaction of the cellular molecules and signaling pathways involved in radioresistance remains incompletely defined. A clinically effective radiosensitizer that overcomes radioresistance has yet to be identified. In this review, we discuss the current status of radiation treatment in GBM, including advances in imaging techniques that have facilitated more accurate diagnosis, and the identified mechanisms of GBM radioresistance. In addition, we provide a summary of the candidate GBM radiosensitizers being investigated, including an update of subjects enrolled in clinical trials. Overall, this review highlights the importance of understanding the mechanisms of GBM radioresistance to facilitate the development of effective radiosensitizers.

Keywords: glioblastoma; radioresistance; radiosensitizer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Timeline of important discoveries and events that led to current imaging techniques for detecting glioblastoma (GBM) and other brain tumors. CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography.
Figure 2
Figure 2
Identified mechanisms of GBM radioresistance. Tumor microenvironment, hypoxia, metabolic alterations, glioma stem cells, tumor heterogeneity, microRNAs, and alteration in cell cycle regulation and DNA damage repair are the most well-defined factors involved in GBM radioresistance. Created with BioRender (Science Suite Inc., Toronto, ON, Canada).
Figure 3
Figure 3
GSCs can self-renew, initiate tumors, and survive radiotherapy. The cells that survive radiotherapy can give rise to a population of cells that are resistant to radiation. Created with BioRender (Science Suite Inc., Toronto, Ontario, Canada).
See this image and copyright information in PMC

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