One of the most difficult cancers to treat is that which has spread to the brain. The main obstacle in delivering chemotherapy to brain tumors is the blood-brain barrier, which prevents harmful substances from entering the brain from the bloodstream, but unfortunately, it also blocks therapeutic agents. However, a newly identified protein has been shown to cross this protective barrier safely and deliver treatment directly to cancerous tumor cells in a preclinical study. The results, published in Nature Nanotechnology, may help doctors target brain tumors that have been previously unreachable by chemotherapy.

The novel protein, known as HER3, was engineered by researchers at Cedars-Sinai Cancer (Los Angeles, CA, USA) and is found on the blood-brain barrier, enabling their tumor-targeting protein to move from the bloodstream into the brain. The researchers conducted experiments using an innovative blood-brain barrier "organ chip." This lab device is designed by transforming small groups of induced pluripotent stem cells into blood vessel cells and brain cells, arranging them in a pattern that mimics the human brain. When the researchers introduced their protein into the blood vessel section of the chip, they observed it crossing over into the brain matter. When they blocked the HER3 proteins, the tumor-targeting proteins were unable to cross, suggesting that HER3 plays a role in their passage from the bloodstream into the brain.

HER3 is also found on the surface of various cancer cells, particularly in tumors that have metastasized to the brain. In experiments with laboratory mice, the tumor-targeting proteins directly attacked HER3-positive tumors, slowing their growth without accumulating in other organs. Once inside the tumor cells, the protein uses a unique mechanism to avoid destruction. The protein includes a pinwheel-like structure that prevents digestion. When it enters the tumor cell, the pinwheel opens and allows the protein to break free from its protective shell. When combined with chemotherapy, it delivers a deadly impact on the tumor. These promising results represent a significant step toward developing therapies that could treat advanced tumors with no current treatment options.

“These blood-brain barrier organ chips are the next best thing to experiments in humans,” said Clive Svendsen, PhD, executive director of the Board of Governors Regenerative Medicine Institute at Cedars-Sinai and a co-author of the study. “They allow us to create the ideal conditions for testing therapies such as this one. We can even use the patient’s own stem cells and make personalized organ chips to test how the drug may work for each person.” 

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