Sonodynamic Therapy for the Treatment of Intracranial Gliomas

Abstract

High-grade gliomas are the most common and aggressive malignant primary brain tumors. Current therapeutic schemes include a combination of surgical resection, radiotherapy and chemotherapy; even if major advances have been achieved in Progression Free Survival and Overall Survival for patients harboring high-grade gliomas, prognosis still remains poor; hence, new therapeutic options for malignant gliomas are currently researched. Sonodynamic Therapy (SDT) has proven to be a promising treatment combining the effects of low-intensity ultrasound waves with various sound-sensitive compounds, whose activation leads to increased immunogenicity of tumor cells, increased apoptotic rates and decreased angiogenetic potential. In addition, this therapeutic technique only exerts its cytotoxic effects on tumor cells, while both ultrasound waves and sensitizing compound are non-toxic per se. This review summarizes the present knowledge regarding mechanisms of action of SDT and currently available sonosensitizers and focuses on the preclinical and clinical studies that have investigated its efficacy on malignant gliomas. To date, preclinical studies implying various sonosensitizers and different treatment protocols all seem to confirm the anti-tumoral properties of SDT, while first clinical trials will soon start recruiting patients. Accordingly, it is crucial to conduct further investigations regarding the clinical applications of SDT as a therapeutic option in the management of intracranial gliomas.

From Focused Ultrasound Tumor Ablation to Brain Blood Barrier Opening for High Grade Glioma: A Systematic Review

“…The measurement is made with Cleaved Caspase-3, MIB-1 level, GammaH2Ax in surgical specimen tissue. Another prospective study to be conducted at Besta Institute in Milan will evaluate the safety and feasibility of sonodynamic therapy with 5-ALA in patients with newly diagnosed GBM [ 53 , 54 , 55 ].…”

“…The measurement is made with Cleaved Caspase-3, MIB-1 level, Gamma-H2Ax in surgical specimen tissue. Another prospective study to be conducted at Besta Institute in Milan will evaluate the safety and feasibility of sonodynamic therapy with 5-ALA in patients with newly diagnosed GBM [53][54][55]. Sunnybrook Health Sciences Centre in Toronto is leading three different trials on tumor ablation, BBB opening and Carboplatin delivery through BBB (NCT01473485; NCT03616860; NCT04440358).…”

Current Landscape of Sonodynamic Therapy for Treating Cancer

“…There are various mechanisms by which SDT enhances anti-tumor activity in promoting the change from M2 to M1 macrophages in the tumors [ 22 ]. M1 macrophages are responsible for the inflammatory process by secreting pro-inflammatory cytokines, and they play a role in anti-tumor activity.…”

Intracranial Sonodynamic Therapy With 5-Aminolevulinic Acid and Sodium Fluorescein: Safety Study in a Porcine Model

“…Furthermore, only one insonation protocol was tested in our experimental design for the same reason; however, the parameters employed in the study were derived from previous preclinical experiences (4,19,20,(33)(34)(35)(36), the efficacy of which will be tested in one FDA and on CE approved clinical trial.…”