Functional Precision Medicine Advances Pediatric Brain Tumor Care

Functional precision medicine may offer a faster, more personalized way to guide treatment for pediatric brain tumors, according to Dr. John Crawford, Division Chief of child neurology at Rady Children's Health, Children's Hospital of Orange County.

In an interview with CURE, Crawford explained that this approach combines traditional pathology with molecular data and functional drug screening, which tests treatments directly on a patient’s own tumor cells to identify what may work best.

He noted that tumors can behave differently even when they share the same mutations, making patient-specific testing valuable. This method may also speed up decision-making, with results available in less than a week compared with longer timelines for standard molecular testing.

Crawford added that advances in targeted therapies, immunotherapies and safer biopsy techniques have expanded options for patients, and he encouraged caregivers to prioritize a complete and accurate diagnosis before making treatment decisions.

CURE: For patients and families facing a pediatric brain tumor diagnosis, what should they understand functional precision medicine and how it differs from the traditional way doctors choose treatments?

Crawford: Yes, you know, it's been fun to watch neuro-oncology over the last 20 years as we have gone from largely an under-the-microscope type of diagnosis to looking at the genetics of the cells of origin and what makes these cells grow and divide. And now, where functional precision medicine really comes in is that it utilizes the findings under the microscope, utilizes the molecular aspects of the tumor, and on top of that uses what we call functional drug screening, which is applying a variety of compounds to the patient's own tumor cells to see what the killing power of those drugs is, with the hope of bringing that back to the patient. It's just another bag of tricks we have to treat these tumors, and it's very patient specific.

Brain tumors can vary greatly from patient to patient. How does testing drugs directly on a child's own tumor cells help physicians better identify which treatments may work?

Yes, there's really no such thing as two tumors that are alike. Even those that molecularly share the same mutations behave very differently, which may be due to the age of the patient, the gender of the patient, and other biological characteristics. Functional precision medicine and drug screening are agnostic to that. It's looking at the patient's own cells on the day of surgery to determine what drugs can attack that tumor in a plate. I think it's more patient specific and holds a lot of promise.

Time is often critical for pediatric brain tumor diagnosis. In what ways could functional precision medicine reduce the time it takes to find an effective treatment?

Yes, functional precision medicine really allows for a more rapid diagnosis compared to other molecular technologies we use, whether it's whole exome sequencing, germline sequencing, RNA sequencing, or methylation analysis. All of that can take many days to many weeks. The beauty of functional precision neuro-oncology with drug screening is that results can come back in less than a week, which is critical when you want to act. At Rady Children's Health, we've been able to do drug screening on needle biopsy samples, which has changed the game because now we have more accessible targets we can reach safely with small amounts of tissue. So again, it holds a lot of promise.

Earlier in your career, you weren’t sure a cure for pediatric brain cancer would be possible. What developments in the field have changed your outlook?

It's been so much fun to watch this field. We have all evolved — physicians, researchers, as well as patients and families. What we've learned from patients and families is they want to be proactive; they want a cure. They are staunch advocates and really work hard to move the field forward. Early in my training, 20 years ago, we were generally told never to touch the brain stem — you don't biopsy it, you don't stick needles in it. Now it's standard of care. We're obtaining incredible molecular and functional information from drug screening to further classify tumors and bring treatments to families. Back in the 80s, brain cancer was largely a diagnosis just for neurosurgeons.

They would remove tumors, the children would be radiated, and chemotherapy only came into play later. Now, we have a whole slew of molecular targeted therapies. Early on, I never thought one could swallow a pill and shrink a tumor inside the head — but that's where we are now. There are also exciting advances in immunotherapies, including CAR T-cell therapies and vaccine therapies. The tools we have to treat brain cancer are far more elaborate than before. The day of the hammer and screwdriver is gone; we've got the most up-to-date rechargeable power tools and then some. It's a very exciting time for the field.

Looking ahead, how might functional precision medicine shape the future of pediatric brain tumor care and research in the next decade?

I think functional precision medicine and functional neuro-oncology in general have very large potential. People have done drug screening in the past, but now we integrate that knowledge with an understanding of the biological makeup of tumors. We can be more sophisticated in our approach to the drugs we use. We also consider the blood-brain barrier, which limits how drugs penetrate the brain and tumor. The field is designing drug sensitivity scoring systems to predict a drug’s ability to reach the brain. In addition to identifying targetable drugs, there is promise in using panels of drug sensitivities to classify tumors — like how we look under the microscope or through methylation profiling and genetic sequencing — potentially creating another important classification system.

With pediatric cancers, caregivers are a huge focus. What advice would you have for a caregiver when their child or loved one receives a diagnosis?

I think what I've learned is that every patient and family is unique, and it's not one-size-fits-all. Clinicians need to respect the patient and family journey. I advocate for ensuring the diagnosis is as accurate as possible, using molecular technologies, because every detail matters. Sometimes the hardest part is waiting for the official diagnosis with all the information, but it's critically important. I tell families, let's walk through one door together; with Google and AI, people may go online with a preliminary diagnosis, but we need to ensure we’re on the right path.

Transcript has been edited for clarity and conciseness.

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