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Researcher Profile: Dr. Jim Olson

Tackling Pediatric Cancer on Multiple Fronts

Children, acne and tumors

Drugs are often developed with just one aim in mind. But human tumor tissue cells can help researchers like oncologist Dr. Jim Olson unearth unexpected new uses for old drugs.

Olson’s team specializes in studying rare pediatric tumors, and has been collecting brain tumor tissue from pediatric patients for the past ten years. Pediatric tumors are tough to treat—the tumors are relatively rare, so there isn’t much clinical data on them, and sometimes patients do not live long enough to let researchers thoroughly study the course of their disease.

While searching for drugs that could be repurposed to treat these types of cancers, Olson’s team began considering Acutane, a drug most frequently prescribed for acne. They suspected the drug might inhibit tumor growth, and were surprised to find that it apparently killed tumor cells in a particularly challenging type of brain cancer called medullablastoma. When combined with existing chemotherapy in non-clinical brain tumor studies, Acutane appears to be one of the most effective anti-cancer treatments currently being explored.

Acutane has now entered Phase 3 clinical trials in a world-wide 250-site consortium.  Once the trials wrap up, outcome data will help researchers understand the drug’s therapeutic promise. If successful, a drug once used to help eradicate teenage acne could graduate to beating back high-risk pediatric tumors.

Avatar mice

One stumbling block to smooth progress in pediatric cancer research is that many children’s tumors are so rare, researchers have not been able to create traditional mouse models that replicate these tumors. Creating a mouse model of a human disease is often a cost-effective, safe way to test and prioritize candidate therapies and understand biochemical treatment pathways.

Olson’s team has overcome this stumbling block by using mice that lack the immune response that would reject human cells. Cells from a pediatric patient’s brain tumor can be injected into the mice, creating dozens or hundreds of animals growing the patient’s tumor. These mice, called avatar mice, let Olson and his team test specific drugs on mouse tumors before prescribing them to the child. Treatment is thus very precise, saving valuable time and sparing the patient harsh side effects.

Developing these customized mouse models has been expensive, but Olson plans to distribute them “no strings attached” to researchers around the world treating similar children with rare tumors.

The avatar mice have helped Olson’s team pin-point several promising drug candidates to treat pediatric tumors. He has gathered enough clinical data to interest drugs companies in starting clinical trials using these drugs. Getting these companies’ investment is no small feat, given how few cases of these cancers exist, and how expensive a clinical trial can be.

But not all the credit belongs to the mice. Once promising drugs are tested in mice, experiments can proceed to testing drugs in human tissue specimens. Patients’ willingness to donate tumor tissues, along with their families’ support, has proved crucial as well.  “We really create a family where everybody has a shared vision. Donating tissue is a very important piece,” Dr. Olson says.

Friends and family of cancer patients frequently tour Olson’s lab to peer at cancer cells under the microscope or observe mouse surgeries. Once a year his lab members trade their white coats for kitchen aprons and cook a meal for patients and family members as part of an evening of research updates, presentations, and sometimes even entertainment by former patients. “My feeling,” he says, “is that we’re all in this together. It seems natural we would want to share the enthusiasm and the results.”

Dr. Jim Olson

Toxicity turned against tumors

Dr. Olson has even recruited scorpions into the fight against cancer. One of Olson’s lab projects has concentrated on formulating easier ways for surgeons to see tumors as they operate.

Enter the Israeli Deathstalker scorpion, whose venom contains peptides derived from chlorotoxin.  These peptides possess a special property: when injected into a patient, they hone in on cancerous cells and stick to them while leaving healthy cells alone.  By adding a florescent “tag” to the peptides, this “Tumor Paint” targets cancer cells with molecular tags that light up when exposed to a laser in the operating room and allow the surgeon to remove all of the tumor and as little normal tissue as possible.

Scorpion peptides are now being developed synthetically in the lab, and are advancing toward human clinical trials by the biotechnology company, Blaze Bioscience.

Human biospecimens helped speed up the development of Tumor Paint.  Instead of using traditionally cultured cell lines, Dr. Olson’s team went straight to fresh tissue specimens to perform their experiments. They started with brain tissue, but studies with other tumor types indicate that Tumor Paint may work on other cancers as well, giving surgeons a brilliant way to redefine cancer surgery.

 

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Israeli Deathstalker scorpion