Journal
JOURNAL OF CONTROLLED RELEASE
Volume 345, Issue -, Pages 443-463Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.03.035
Keywords
Preclinical focused ultrasound; Blood-brain barrier; Glioblastoma; Drug delivery; Immunotherapy; Sterile inflammation
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Survival outcomes for patients with glioblastoma multiforme (GBM) have remained poor for the past 15 years, reflecting a clear challenge in the development of more effective treatment strategies. The presence of the blood-brain barrier (BBB) greatly limits the efficacy of systemic therapies for GBM. Focused ultrasound (FUS) shows promise in enhancing drug delivery to infiltrating tumor regions by temporarily disrupting the BBB. This review discusses the current state of preclinical investigations using FUS to enhance drug delivery to intracranial neoplasms and highlights the importance of selecting clinically relevant animal models and standardizing FUS delivery methods for successful clinical translation of this technology.
Survival outcomes for patients with glioblastoma multiforme (GBM) have remained poor for the past 15 years, reflecting a clear challenge in the development of more effective treatment strategies. The efficacy of systemic therapies for GBM is greatly limited by the presence of the blood-brain barrier (BBB), which prevents drug penetration and accumulation in regions of infiltrative tumour, as represented in a consistent portion of GBM lesions. Focused ultrasound (FUS) - a technique that uses low-frequency ultrasound waves to induce targeted temporary disruption of the BBB - promises to improve survival outcomes by enhancing drug delivery and accumulation to infiltrating tumour regions. In this review we discuss the current state of preclinical investigations using FUS to enhance delivery of systemic therapies to intracranial neoplasms. We highlight critical methodological inconsistencies that are hampering clinical translation of FUS and we provide guiding principles for future preclinical studies. Particularly, we focus our attention on the importance of the selection of clinically relevant animal models and to the standardization of methods for FUS delivery, which will be paramount to the successful clinical translation of this promising technology for treatment in GBM patients. We also discuss how preclinical FUS research can benefit the development of GBM immunotherapies.
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