The use of radiosensitizing agents in the therapy of glioblastoma multiforme—a comprehensive review

Abstract

Background Glioblastoma is the most common malignant brain tumor in human adults. Despite several improvements in resective as well as adjuvant therapy over the last decades, its overall prognosis remains poor. As a means of improving patient outcome, the possibility of enhancing radiation response by using radiosensitizing agents has been tested in an array of studies. Methods A comprehensive review of clinical trials involving radiation therapy in combination with radiosensitizing agents on patients diagnosed with glioblastoma was performed in the National Center for Biotechnology Information’s PubMed database. Results A total of 96 papers addressing this matter were published between 1976 and 2021, of which 63 matched the subject of this paper. All papers were reviewed, and their findings discussed in the context of their underlining mechanisms of radiosensitization. Conclusion In the history of glioblastoma treatment, several approaches of optimizing radiation-effectiveness using radiosensitizers have been made. Even though several different strategies and agents have been explored, clear evidence of improved patient outcome is still missing. Tissue-selectiveness and penetration of the blood–brain barrier seem to be major roadblocks; nevertheless, modern strategies try to circumvent these obstacles, using novel sensitizers based on preclinical data or alternative ways of delivery.

Beyond fluorescence-guided resection: 5-ALA-based glioblastoma therapies

“…With repetitive administration, there is a risk of accumulation of the substance with an increased risk of developing side effects, leading to a debate in terms of biosafety [ 40 ]. Some in vitro and in vivo studies including clinical trials have investigated the efficacy of different radiosensitizing agents in the treatment of malignant gliomas: nitroimidazoles, nicotinamide and carbogen, tipifarnib, efaproxiral, tirapazamine, halogenated bromodeoxyuridine and iododeoxyuridine, poly (ADP-ribose) polymerase proteins, motexafin gadolinium, difluoromethylornithine, interferon-alpha-2a, lovastatin, and 5-ALA [ 26 ].…”

Recent Metal Nanotheranostics for Cancer Diagnosis and Therapy: A Review

“…Motexafin gadolinium (MGd), a metallotexaphyrin, is a compound of gadolinium and an expanded porphyrin that can enhance the cytotoxic effects of radiation through several mechanisms relying on the additional generation of reactive oxygen species (ROS) that catalyze the oxidation of intracellular-reducing metabolites and interference with repair mechanisms of radiation-induced damage, which lead to increased cell death. Motexafin gadolinium showed great promise for multifunctional theranostic applications, especially for glioma treatment, and so far, two-phase clinical studies combined with standard radiation treatment have been established [43]. The research results indicated that, in addition to exploiting GdNPs as a positive MR imaging T 1 contrast agent, they had been identified as valued theranostic sensitizers for radiation therapy [44,45].…”

Nanomaterials as Theranostic Agents for Cancer Therapy

“…Motexafin gadolinium exhibited considerable potential in the realm of multifunctional theranostic applications, mainly in the treatment of gliomas. Until now two phase clinical studied have been initiated, using this compound with conventional radiation treatment . GdNPs were used as a positive MR imaging contrast T1 as well as being recognized as valuable theranostic sensitizers for radiation therapy. , Free GdNPs are not being used for clinical purposes as they are toxic; hence, they are used as an organic chelating compound.…”