Ultrasound-induced blood-brain barrier disruption for the treatment of gliomas and other primary CNS tumors.

Author: Beccaria K1, Canney M2, Bouchoux G2, Desseaux C2, Grill J3, Heimberger AB4, Carpentier A5
1Department of Pediatric Neurosurgery, Necker Enfants Malades Hospital, APHP, Paris 5 University, Paris, France. Electronic address: kevin.beccaria@aphp.fr.
2CarThera, Institut Du Cerveau et de La Moelle épinière (ICM), Paris, F-75013, France.
3Department of Pediatric Oncology, Gustave-Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France; UMR8203 "Vectorologie et Thérapeutiques Anticancéreuses," CNRS, Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
4Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, USA.
5Department of Neurosurgery, Sorbonne Université, UPMC Univ Paris 06, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié-Salpêtrière, Paris, France.
Conference/Journal: Cancer Lett.
Date published: 2020 Feb 26
Other: Pages: S0304-3835(20)30075-6 , Special Notes: doi: 10.1016/j.canlet.2020.02.013. [Epub ahead of print] , Word Count: 193

The treatment of primary brain tumors, especially malignant gliomas, remains challenging. The failure of most treatments for this disease is partially explained by the blood-brain barrier (BBB), which prevents circulating molecules from entering the brain parenchyma. Ultrasound-induced BBB disruption (US-BBBD) has recently emerged as a promising strategy to improve the delivery of therapeutic agents to brain tumors. A large body of preclinical studies has demonstrated that the association of low-intensity pulsed ultrasound with intravenous microbubbles can transiently open the BBB in a localized manner. The safety of this technique has been assessed in numerous preclinical studies in both small and large animal models. A large panel of therapeutic agents have been delivered to the brain in preclinical models, demonstrating both tumor control and increased survival. This technique has recently entered clinical trials with encouraging preliminary data. In this review, we describe the mechanisms and histological effects of US-BBBD and summarize the preclinical studies published to date. We furthermore provide an overview of the current clinical development and future potential of this promising technology.

Copyright © 2020. Published by Elsevier B.V.

KEYWORDS: blood-brain barrier; brain tumors; glioblastoma; low-intensity pulsed ultrasound; ultrasound

PMID: 32112904 DOI: 10.1016/j.canlet.2020.02.013