KAIST researchers who conducted the study. From left in the back row, clockwise: Kang Na-young, master's student; Jung Jin-woo, doctoral student; Professor Ahn Song-i; and Ryu Min-su, doctoral student. [KAIST]
KAIST researchers who conducted the study. From left in the back row, clockwise: Kang Na-young, master's student; Jung Jin-woo, doctoral student; Professor Ahn Song-i; and Ryu Min-su, doctoral student. [KAIST]

South Korean researchers have developed a technology that replicates a patient's tumor cells and brain vascular environment on a chip, enabling advance prediction of individual treatment responses.

KAIST announced Tuesday that a team led by Professor Ahn Song-i of its mechanical engineering department — working with Professor Ahn Jung-ho of Sungkyunkwan University, Professor Lim Jae-jun of Bundang Cha Hospital and Professor Kang Yun-jung of Cha University of Medicine and Science — has developed a patient-specific blood-brain tumor barrier (BBTB) chip capable of predicting treatment responses in glioblastoma patients.

Glioblastoma is one of the most lethal malignant brain tumors. Cancer cells spread rapidly into normal brain tissue, and the tumor's characteristics vary from patient to patient, making treatment difficult.

The brain contains a blood-brain barrier that blocks harmful substances in the bloodstream from entering the brain. That same barrier, however, also impedes anticancer drugs from reaching the tumor in sufficient concentrations. When glioblastoma develops, the vascular barrier surrounding the tumor changes as well — and the extent and nature of that change differ among patients, which is one reason the same treatment can produce different outcomes in different individuals.

Conventional approaches to predicting treatment responses in glioblastoma patients have relied primarily on tumor genetics and biomarkers. Those methods alone have proven insufficient for capturing the varying vascular environments around each patient's tumor or for gauging actual drug responses.

To address this limitation, the research team reproduced on a chip not only the patient's tumor but also the vascular barrier — the pathway anticancer drugs must traverse to reach the tumor.

Glioblastoma cells, brain vascular endothelial cells and astrocytes obtained from patients were co-cultured inside a small microfluidic chip, creating an environment that closely mimics the boundary where tumor and normal brain tissue meet. The chip was also designed to accommodate perivascular cells and immune cells, allowing for a more precise recreation of the vascular environment surrounding a brain tumor in a living person.

The team fabricated individual BBTB chips modeled on tumor cells from three different glioblastoma patients, then applied temozolomide (TMZ) and bevacizumab (BEV) — drugs used in glioblastoma treatment — to compare treatment responses across patients.

A schematic of patient-specific drug evaluation using the microfluidic blood-brain tumor barrier chip. [KAIST]
A schematic of patient-specific drug evaluation using the microfluidic blood-brain tumor barrier chip. [KAIST]

Patients whose genetic tests had predicted similar treatment responses showed distinct differences in vascular barrier characteristics and drug responses on the chip. The per-patient treatment responses observed on the chip closely matched actual clinical outcomes — suggesting that even when genetic profiles are similar, treatment responses can vary depending on the state of the vascular barrier surrounding each patient's tumor, and that a patient-specific chip can reveal those differences.

"This research is significant in that it presents a platform capable of evaluating patient-specific treatment responses realistically by simultaneously reproducing patient-derived tumor cells and the blood-brain tumor barrier," Professor Ahn said. "We hope to validate the approach in a larger patient population and develop it into a preclinical evaluation platform for establishing personalized treatment strategies and advancing drug development for glioblastoma patients."

She added, however, that the study remains a proof-of-concept, with chip results confirmed to align with actual clinical outcomes in only three patients. "Further research will be needed to improve predictive accuracy by securing experimental data from multiple institutions and larger patient cohorts," she said.

The findings were published in Small, an international academic journal covering materials science and nanotechnology.


nbgkoo@heraldcorp.com