Lighting up a new way to treat pediatric brain cancer

Dr. Jim Olson, a physician at Seattle Children’s Hospital and research scientist at the Fred Hutchinson Cancer Research Center, likes to share stories of the patients and people in his life who provide a motivation for his research on brain tumor treatments.

At a recent Town Hall presentation, Olson shared a recent experience about his own mother, who was receiving radiation treatment for a cancer at the base of her brain. The physicians were attaching a metal frame the size of a football helmet to her head “the same way you would attach a Christmas tree stand to your Christmas tree,” by turning screws on the frame until they touched her skull and stuck. As Olson was observing this, he thought,

The way that we treat cancer patients today is barbaric. This is cutting edge, this is the leading edge of the best in the world, and we’re still frying cancer, we’re still putting poisons into people’s bloodstream.

In his own practice, Olson is all too familiar with the challenges of curing brain cancer. In addition to radiation and chemotherapy treatments, brain cancer is commonly treated with surgery to remove malignant tumors. Surgery is extremely difficult because the work must be very exact. Leave some of the tumor behind, and the cancer can return; cut too far, and damage to the brain may cause devastating effects to the patient. Surgeons rely on cues like color, texture, and blood supply to identify the tumor, but often times the cancerous tissue looks identical to the healthy tissue.

Wouldn’t it be easier if there was a way that the brain tumor could “light up,” so surgeons could tell exactly where to cut?

With hard work and a lot of support from the community, Olson and his colleagues have been trying to answer this question. In a pursuit that could forever change how brain surgery is performed, Olson’s team has engineered a new molecule called “tumor paint.”

Tumor paint is a molecule that enters cancerous cells and lights up, giving surgeons a much better way to distinguish the location of the tumor.

tumor paint
Tumor paint indicating the location of breast cancer in a dog, whose family asked to be treated during the first clinical trials of tumor paint. Although the surgeons knew the large tumor near the bottom was cancerous, the tumor paint was also able to show three additional, smaller areas with cancer that may have otherwise been missed. (Photo courtesy Blaze Bioscience).

How did Olson’s team create tumor paint? First, they looked for a molecule that would be able to find cancer in the brain. This is challenging because the brain is naturally protected by the Blood Brain Barrier, a special layer of tissue that prevents most chemicals in the blood from affecting the brain. Molecules that are able to cross this barrier and encounter a tumor are rare.

The team looked through scientific research publications and considered thousands of candidates that might be useful. Finally, they found a peptide (miniprotrin) called chlorotoxin, which is present in the venom of the Deathstalker scorpion (Leiurus quinquestriatus)

Deathstalker scorpion in captivity. (CC BY-SA 3.0) Anatolii Kokoza.
The Deathstalker scorpion, shown here eating a cricket, is an unknowing aid to the fight against cancer. (CC BY-SA 3.0) Anatolii Kokoza.

A researcher at the University of Alabama had been studying how chlorotoxin peptides have a high affinity for a certain kind of chloride ion channel. These ion channels are present on the surface of cancerous brain cells but not healthy brain cells.

Olson tested chlorotoxin right away, to see if it would uniquely light up tumor cells and not healthy cells. They attached a little “molecular flashlight” to the chlorotoxin peptide and injected it into a mouse with a brain tumor:

I told [my colleague], “If the cancer lights up, we keep going, and if it doesn’t light up, we go back to the drawing board.”

…An hour later, the cancer was glowing brightly, and the rest of the mouse was not glowing. I’ve never had that happen, where an experiment worked for the first time that I did it.

Olson borrowed mice with different types of cancers, like skin, breast, and prostate cancer, and injected them with the chlorotoxin conjugate. All the tumors lit up, just like the brain cancer. “Tumor paint” was born.

Although there are still several hurdles to pass before tumor paint can be used in treatment on humans, Olson is optimistic that in ten years, surgeons will wonder how they ever managed to do surgery without aids like tumor paint.

Using knowledge he gained from engineering tumor paint, Olson has also started Project Violet, named after an inspirational young girl who had a very serious, untreatable brain cancer. Olson hopes that other peptides similar to chlorotoxin can be used to create better, safer treatments for patients and children with brain tumors.

The Science Slug

More information about Jim Olson and his work



An adaptation of this article was published on the Neuroscience for Kids website by Dr. Eric Chudler.


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