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Three-Dimensional Organoid Models May Help Improve Drug Therapy for Brain Tumors

In their study, Drs. Hubert, Sundar and Shakya, and colleagues suggest that organoids can model patient-like drug resistance similar to that seen in human brain tumors.

12/22/2021




In a new study related to drug resistance, researchers from the Department of Biomedical Engineering show that 3D organoids (organ-like structures that are grown in the lab to mimic human tissue) offer a realistic platform to test potential medications against glioblastoma. Their findings were recently published in Translational Oncology.

Glioblastomas are the most common primary malignant brain tumor and the least amenable to drug treatment. One reason, according to Christopher Hubert, PhD, senior author of the study, is that glioblastomas are heterogeneous—they contain many different types of cancer cells in the tumor environment, all of which behave differently from each other and have different drug sensitivities. This makes it difficult to kill all of the tumor cells with one drug. “These circumstances create a situation in which drug resistance is a major problem,” said Dr. Hubert.

Organoids, aka “mini-tumors,” may provide a treatment map

Dr. Hubert noted that organoids, by remaking the diverse array of cell types in glioblastoma tumors, can help determine the degree and specificity of drug resistance—i.e., which drugs will work best against the tumor— and therefore inform personalized treatment regimens for each patient.

In their study, the researchers collected brain tumor specimens from adult and pediatric patients following surgery and created organoids from them. They subjected the organoids and the patient brain tumor samples to various medications that are currently used to treat glioblastomas, as well as four different chemotherapy drugs, including some standard and experimental. They found that the organoids were usually more resistant to these therapies than the same cells from the same patient’s brain tumor that were grown using traditional methods on plastic dishes. In some cases, however, the researchers found exceptions where certain patient samples had unique sensitivities or resistance to specific drug candidates. These effects could also be pinpointed to specific environments within the organoids.

“We believe that the diverse cell behavior, support structure and environment within brain tumor organoids provide a protective mechanism against cell death from many of these therapies,” said Dr. Hubert. “Going forward, we are using organoids to model and target the pieces of each separate type of tumor cell with individual drugs. This will enable us to create drug combinations that more completely destroy the whole tumor.” 

The future of glioblastoma treatment?

“Because our novel organoid cultures recreate a wide range of the diverse cells within a brain tumor, they may be a key tool for assessing drug sensitivity and for learning how responsive a tumor may be to drug treatment,” Dr. Hubert said. “In particular, they can help uncover drug resistance that only arises when cancer is grown in a physiologic 3D environment. Organoids can help us better understand the brain tumor environment, how the cancer cells adapt to their location and surroundings, and how this adaptation and diversity can make glioblastoma so difficult to treat. This has great potential for future research.”

Drs. Sundar and Shakya are both members of Dr. Hubert’s lab. This study was supported by the National Institutes of Health and the American Brain Tumor Association.

 




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