Cancer researchers unite in the battle against a deadly form of brain cancer affecting children

Researchers from the Fralin Biomedical Research Institute at Virginia Tech have partnered with Children's National Hospital to collaborate on a groundbreaking initiative aimed at treating life-threatening brain tumors using ultrahigh frequency sound waves.

A collaborative effort has formed among cancer researchers to combat the devastating effects of diffuse midline glioma (DMG), a highly fatal brain cancer that primarily affects children. Spearheading this endeavor is Javad Nazarian, a leading investigator at Children's National Hospital, who is joined by a multi-institutional team.

Their focus lies in exploring the potential of an emerging technology called focused ultrasound to fight DMG. By leveraging this innovative approach, the researchers aim to create a temporary pathway through the body's protective blood-brain barrier, facilitating the targeted delivery of cancer medication.

The team is comprised of accomplished experts in various fields. Eli Vlaisavljevich, from the Virginia Tech Cancer Research Alliance, brings expertise as a designer and developer of focused ultrasound technology, while Jennifer Munson specializes in utilizing 3D models to study brain tumors, contributing her proficiency in focused ultrasound instrumentation and tissue engineering.

Additionally, Columbia University's Cheng-Chia Wu, a principal investigator with extensive experience in combining focused ultrasound with radiation and immunotherapy for both pediatric and adult brain tumors, further strengthens the team's capabilities. Wu has notably led the world's first clinical trial employing focused ultrasound in children with relapsed DMG.

''Bringing this expertise together will advance this promising platform for treatment of pediatric brain tumors. Individually, we progress slowly or we may fail. Together, we will be able to better understand how to treat these tumors and accelerate their delivery to the clinic."

Children's National Hospital has received a generous $672,000 grant from the SebastianStrong Foundation, a nonprofit organization dedicated to raising awareness about childhood cancers and supporting the development of safer and more targeted treatments and cures. This funding will facilitate the ongoing research efforts in collaboration with Virginia Tech's Fralin Biomedical Research Institute.

The project at Virginia Tech builds upon previous research supported by the Seale Innovation Fund grant, which was awarded to Munson, Vlaisavljevich, and Nazarian. The earlier study focused on utilizing focused ultrasound and sonodynamic therapy, a noninvasive treatment approach that aims to reduce the number of cancer cells and impede future tumor growth.

Munson, an associate professor at the Fralin Biomedical Research Institute and the Department of Biomedical Engineering and Mechanics in the College of Engineering, emphasizes the importance of delivering effective treatment doses to these aggressive and invasive tumors in children without causing harm or hindering their development. The ultimate goal is to target the tumors with precision while minimizing any potential damage.

Within Munson's laboratory, an initiative is underway to create 3D cell culture models incorporating DMG tumor cells obtained from patients at Children's National Hospital. These meticulously engineered tissue models of the tumor microenvironment hold the potential to unravel the mechanisms behind tumor recurrence and identify the most optimal treatments for eliminating them.

"Our goal is ultimately to develop a personalized medicine approach in which we can take a patient's tumor, build a model of that tumor in a dish, test drugs on it, and tell a clinician which therapy will work best to treat it," Munson said.

Simultaneously, Vlaisavljevich, an associate professor in the Department of Biomedical Engineering and Mechanics, is dedicated to designing focused ultrasound instrumentation that can operate effectively in both cell cultures and living systems. At Virginia Tech's Therapeutic Ultrasound and Noninvasive Therapies lab, Vlaisavljevich explores the potential of a technology known as histotripsy. This technique involves generating cavitation bubbles within tissue, which, upon rupture, have the capability to selectively destroy targeted tumors.

One of the key challenges in brain cancer treatment lies in delivering therapeutic agents to the intended target area. Vlaisavljevich highlights this issue, particularly in the context of the brain, stating, "The problem is delivery - actually getting the drug to the target. That's difficult in the brain." However, the promising aspect of focused ultrasound is its potential to enhance drug delivery by utilizing microbubbles to temporarily disrupt the blood-brain barrier, allowing medications to reach tumors that are typically challenging to access using other therapeutic approaches.

DMG tumors typically originate near the spinal cord in the base of the brain and spread throughout the central nervous system via cerebrospinal fluid, posing difficulties for surgical interventions, radiation, and chemotherapy. Furthermore, these tumors have the tendency to invade neighboring tissue and extend beyond the visible extent detectable by MRI or during surgical procedures, as outlined by the National Cancer Institute.

Vlaisavljevich explains that their role in the project is focused on conducting fundamental scientific research. Their aim is to investigate how to customize this therapy to maximize its effectiveness against cancer cells while minimizing off-target effects and reducing toxicity.

The urgency for research into pediatric cancer is underscored by Oscar Ortiz, the founder of the SebastianStrong Foundation, established in 2017 in memory of his son Sebastian, who lost his life to cancer. Ortiz emphasizes the pressing need for more targeted drugs and treatments specifically designed for childhood cancer, as compared to the significant advancements made in adult cancer treatments over the past few decades.

The study will be carried out across various locations, including the Virginia Tech labs in Blacksburg and the Fralin Biomedical Research Institute in Roanoke. Additionally, ongoing research for the project is being conducted at the Children's National Research & Innovation Campus in Washington, D.C.

In complementary research efforts, Kathleen Mulvaney and Jia-Ray Yu, both assistant professors affiliated with the Fralin Biomedical Research Institute, are actively pursuing strategies to identify and deliver innovative therapeutic interventions at the molecular level to treat childhood brain cancers. Mulvaney focuses on exploiting vulnerabilities in glioblastoma and malignant peripheral nerve sheath tumors, two rare but deadly cancers affecting children. On the other hand, Yu explores the epigenetic and molecular foundations of diffuse midline glioma in search of potential new therapies. Together, their objective is to develop parallel and collaborative approaches to treat a broad range of pediatric brain cancers.

Source : Virginia Tech