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Ultrasound-Enhanced Drug Delivery in Pediatric Neuro-Oncology: A New Therapeutic Strategy
Elora Weber1, Christian A Smith1, Cynthia Hawkins1,2,3
1Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada.
Abstract:
Pediatric brain tumors are highly prevalent and remain one of the leading causes of cancer-related deaths in children. There are numerous different brain tumor types that are now well characterized by magnetic resonance imaging (MRI), patient clinical course, and neuropathological and molecular genetic alterations. One of the challenges with treating pediatric brain tumors with systemic chemotherapy is the inability of several chemotherapeutic agents to cross the blood-brain barrier (BBB), which serves as a protective mechanism for neuronal homeostasis. The BBB primarily comprises microvascular endothelial tight junctions. Controlling BBB permeability to allow for therapeutics to cross and combat brain tumors is now possible using MR-guided focused ultrasound (MRgFUS). In this approach, microbubbles are administered intravenously prior to MRgFUS BBB disruption at the targeted tumor site in the brain. In the presence of MRgFUS, the microbubbles in the brain capillaries oscillate and temporarily disrupt the BBB, enabling systemically administered chemotherapy drugs to cross at the targeted site. In this review, we provide evidence supporting the use of MRgFUS BBB disruption to treat brain tumors in animal models and in ongoing human clinical drug trials. We conclude with efforts to harness the potency of the immune system using MRgFUS against pediatric brain tumors.
Insights
Magnetic resonance-guided focused ultrasound (MRgFUS) temporarily disrupts the blood-brain barrier (BBB), allowing chemotherapy to reach pediatric brain tumors. This innovative approach shows promise in preclinical models and human trials for treating these challenging cancers.
Area of Science:
- Oncology
- Neurology
- Medical Imaging
- Biotechnology
Background:
- Pediatric brain tumors are a significant cause of childhood cancer mortality.
- The blood-brain barrier (BBB) impedes systemic chemotherapy delivery to brain tumors.
- Current treatment challenges include overcoming the BBB's protective function.
Purpose of the Study:
- To review the evidence for using MR-guided focused ultrasound (MRgFUS) to disrupt the BBB.
- To evaluate MRgFUS as a method for enhancing chemotherapy delivery for pediatric brain tumors.
- To explore the potential of MRgFUS in conjunction with immunotherapy for brain tumors.
Main Methods:
- MR-guided focused ultrasound (MRgFUS) is used to induce temporary BBB opening.
- Intravenous microbubbles are administered to facilitate MRgFUS-mediated BBB disruption.
- Chemotherapeutic agents are administered systemically to cross the disrupted BBB at the tumor site.
Main Results:
- MRgFUS BBB disruption enables enhanced delivery of systemic chemotherapy to targeted brain regions.
- Evidence from animal models supports the efficacy of this approach.
- Ongoing human clinical trials are investigating the safety and effectiveness in patients.
Conclusions:
- MRgFUS BBB disruption is a viable strategy for improving chemotherapy penetration in pediatric brain tumors.
- This technique holds potential for improving treatment outcomes in pediatric neuro-oncology.
- Future research will focus on leveraging MRgFUS for immune system activation against brain tumors.
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