Improved Brain Chip Could Advance Cancer Precision Medicine

Researchers at the University of Houston have improved a microfluidic brain chip that allows multiple-simultaneous drug administration and massive parallel testing of drug response for patients with glioblastoma (GBM).

GBM is the most common malignant brain tumor, accounting for 50 percent of all cases. These patients have a five-year survival rate of just 5.6 percent.

Typically, providers administer chemotherapy drugs to patients, evaluate the effects of these drugs for several months, and switch the patient to another drug if the first is found ineffective. This new brain chip can determine the optimal drug combination in as little as two weeks.

To improve the brain chip, researchers took a piece of a tumor biopsy, cultured it, and put it in the chip. Then, they added chemotherapy drugs to the chip’s microvalves to determine the best drug combination, as well as the specific proportion, that kills the most tumor cells.

The team cultured 3D tumor spheroids, or clusters, from GBM cell lines as well as patient-derived GBM cells in vitro and evaluated the effect of the combination of Temozolomide and a nuclear factor-KB inhibitor on tumor growth.

To minimize any sample loss in vitro, the team improved their existing brain cancer chip system by adding an additional laminar flow distribution layer. This reduces sample loss during cell seeding and prevents spheroids from escaping, which allows the spheroids to form uniformly throughout the chip for consistent drug testing between each spheroid.

“The new chip generates tumor spheroids, or clusters, and provides large-scale assessments on the response of these GBM tumor cells to various concentrations and combinations of drugs. This platform could optimize the use of rare tumor samples derived from GBM patients to provide valuable insight on the tumor growth and responses to drug therapies,” reports Metin Akay, John S. Dunn Endowed Chair Professor of Biomedical Engineering and department chair. 

Using multiple drugs to treat patients with cancer has emerged as a promising way to improve outcomes. A research team from the University of California San Diego School of Medicine recently found that using multi-drug therapies boosted health among individuals with therapy-resistant cancers, indicating that combination therapies could enhance cancer precision medicine.

“Personalized, multi-drug therapies have not been used as standard treatment because there are concerns about the safety of administering drug combinations that have not been previously studied together,” said first author and co-principal investigator Jason K. Sicklick, associate professor of surgery at UC San Diego School of Medicine and surgical oncologist at Moores Cancer Center at UC San Diego Health.

“Yet personalized combinations are necessary since no two tumors are exactly the same and so no two regimens will be the same. Our findings demonstrate that this approach is feasible and safe when patients are monitored closely and started on reduced doses.”

With this new brain chip, researchers at the University of Houston are improving the use of combination therapies for cancer and advancing precision medicine for the disease.

“When we can tell the doctor that the patient needs a combination of drugs and the exact proportion of each, this is precision medicine,” said Metin Akay.

The results have promising implications for the future of cancer care.

“Our study revealed that these drugs have synergistic effects in inhibiting spheroid formation when used in combination, and suggests that this brain cancer chip enables large-scale, inexpensive and sample-effective drug screening to 3D cancer tumors in vitro. Further, this platform could be applied to related tissue engineering drug screening studies,” said assistant professor Yasmine Akay.