Abstract
Simple SummaryNumerous mechanisms of glioblastoma (GBM) radioresistance have been identified but have not yet resulted in development of effective radiosensitizer that can increase the efficacy of radiotherapy. In this review, the authors review the mechanisms of GBM radioresistance along with current status of radiation treatment and imaging techniques used in GBM diagnosis and radiotherapy. In addition, they summarize the current GBM radiosensitizers that are being investigated or enrolled in clinical trials. This review emphasizes on the importance of developing an effective radiosensitizers to increase the outcome of GBM radiotherapy. The authors highlight the importance of discovering of novel mechanism(s) of GBM radioresistance that will lead in developing an effective radiosensitizer.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.
Highlights
Glioblastoma (GBM) is the most common adult primary malignant brain tumor and is the most lethal [1,2]
This review presents a brief synopsis of historic advances in GBM diagnosis and treatment, along with reported findings from pre-clinical studies and the clinical trials of candidate radiosensitizers in GBM
Many clinical trials with different chemotherapeutic and recently immunotherapeutic agents administered as single agents or in combinational therapy have been conducted for recurrent GBM [57,74,75,76,77,78], yet none of these combinations has reliably improved survival, highlighting the urgency to find new GBM treatment options
Summary
Glioblastoma (GBM) is the most common adult primary malignant brain tumor and is the most lethal [1,2]. 14.6–20.5 months, respectively, even with a highly aggressive standard-of-care treatment consisting of maximum safe surgical resection, radiation therapy, and chemotherapy [3,4,5,6,7,8]. In light of this grim prognosis, substantial effort has been invested to improve the overall survival of patients with GBM. Over the last decade, all preclinical strategies that have shown promise for improving the outcome of GBM treatments have failed to provide an overall survival benefit in large randomized clinical trials [4,5,6,9,10]. This review presents a brief synopsis of historic advances in GBM diagnosis and treatment, along with reported findings from pre-clinical studies and the clinical trials of candidate radiosensitizers in GBM
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