Rice-Sized Device Tests 20-Plus Brain Cancer Treatments at Once


Summary: Researchers developed a minuscule device, akin to a grain of rice in size, that can simultaneously test numerous treatments for challenging brain cancers like gliomas. Implanted into a patient’s tumor during surgery and removed afterward, the device offers real-time insights on drug effects on the tumor microenvironment. By doing so, it circumvents the limitations of current testing methods, offering a more personalized approach to treatment.

Key Facts:

  1. The innovative device can test the effects of up to 20 drugs on a patient’s brain tumor in real-time during surgery, without causing any adverse effects.
  2. Gliomas affect around 20,000 people in the U.S. annually and are one of the deadliest and most challenging brain cancers to treat.
  3. The researchers aim to optimize glioma therapy by understanding the tumor’s reaction to drugs in real-time, within the patient’s body, rather than in lab conditions.

Source: Brigham and Women’s Hospital

The shape and size of a grain of rice, the new device can conduct dozens of experiments at once to study the effects of new treatments on some of the hardest-to-treat brain cancers.

Researchers from Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, have designed a device that can help test treatments in patients with gliomas, a type of tumor that originates in the brain or spinal cord.

The device, which is designed to be used during standard of care surgery, provides unprecedented insight into the effects of drugs on glioma tumors and caused no adverse effects on patients in a phase 1 clinical trial.

Results from the pilot clinical trial for the device are published in Science Translational Medicine.

“In order to make the greatest impact on how  we treat these tumors, we need to be able to understand, early on, which drug works best for any given patient,” said co-principal investigator and co-corresponding author Pierpaolo Peruzzi, MD, PhD, an assistant professor in the Department of Neurosurgery at Brigham and Women’s Hospital.

“The problem is that the tools that are currently available to answer this question are just not good enough. So we came up with the idea of making each patient their own lab, by using a device which can directly interrogate the living tumor and give us the information that we need.” 

About 20,000 people in the U.S. each year are diagnosed with gliomas, a type of tumor that affects the brain and spinal cord. Gliomas are also among the deadliest brain cancers and are notoriously difficult to treat.

One challenge in developing targeted therapies for glioma is that it can be difficult to test many different combinations of drugs in tumor cells, because it’s only possible to treat patients with one approach at a time. This has been a significant barrier for hard-to-treat cancers like gliomas, for which combination therapies are a promising avenue.

Peruzzi worked closely with co-principal investigator Oliver Jonas, PhD, an associate professor in the department of Radiology at the Brigham, to develop a device that can work around some of the barriers to precision medicine in gliomas. These microdevices are implanted in a patient’s tumor during surgery and removed before the surgery is complete.

“It’s important that we are able to do this in a way that best captures the features of each patient’s tumor and, at the same time, is the least disruptive of the standard of care,” said Peruzzi. “This makes our approach easy to integrate into patients’ treatment and allows its use in real life.”

In the time the device is implanted—about 2-3 hours—it administers tiny doses of up to 20 drugs into extremely small areas of the patient’s brain tumor. The device is removed during the surgery and the surrounding tissue is returned to the lab for analysis.

Because the device works while the tumor is still in the body, conducting experiments this way gives unparalleled ability to assess the effects of drugs on the tumor microenvironment, the cells immediately surrounding cancer cells that can make up almost half the mass of a tumor.

“This is not in the lab, and not in a petri dish,” said Peruzzi. “It’s actually in real patients in real time, which gives us a whole new perspective on how these tumors respond to treatment.”

In the current study, the researchers tested their device on six patients undergoing brain surgery to remove a glioma tumor. None of the patients experienced any adverse effects from the device, and the researchers were able to collect valuable biological data from the devices, such as how the response changes based on drug concentrations, or what molecular changes each drug produces in the cells.

While the study demonstrated that the device was safe and could be easily incorporated into surgical practice, the researchers are still working on determining the exact ways the data it gathers should be used to optimize glioma therapy.

The researchers are currently conducting a two-stage version of their procedure in which patients receive the device through minimally invasive surgery 72 hours before their main surgery.

“We’re optimistic that this is a new generation approach for personalized medicine,” said Peruzzi. “The ability to bring the lab right to the patient unlocks so much potential in terms of the type of information we can gather, which is new and exciting territory for a disease that has very few options at present.”

Disclosures: Pierpaolo Peruzzi is co-founder and on Board of Directors of Ternalys Therapeutics. He is a named inventor on microRNA-related patent PCT/US2019/029988. Jonas is a coinventor of the IMD technology (U.S. patent no. US10390702B2) and is a consultant with compensation (non-equity) to Kibur Medical. Co-author Antonio Chiocca is a named inventor on patents related to oncolytic HSV1 (U.S. patent nos. US10,806,761B2 US10,232,002B1, and US2017/0015757A1) and noncoding RNAs (PCT/US2019/029988).

Funding: This study was supported by grants from the National Institutes of Health (R37CA224144, P41EB028741) and the National Institute of Neurological Disorders and Stroke (1R01NS116144).

About this brain cancer and neurotech research news

Author: Angela Christoforos
Source: Brigham and Women’s Hospital
Contact: Angela Christoforos – Brigham and Women’s Hospital
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Intratumoral drug-releasing microdevices allow in situ high throughput pharmaco phenotyping in patients with gliomas” by Pierpaolo Peruzzi et al. Science Translational Medicine


Abstract

Intratumoral drug-releasing microdevices allow in situ high throughput pharmaco phenotyping in patients with gliomas

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades.

With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling.

These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours).

None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens.

Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide.

From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow.



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