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When it comes to research, Joanna Gell, MD, thrives on a challenge. That’s why she has chosen one of the toughest kinds of tumor for her opponent: intracranial germ-cell tumors.

When a fetus starts to develop, each cell gets an assignment for the kind of cell it’s going to be—blood, muscle, bone, etc. And most cells go straight to work becoming that singular type. But germ cells, the ones that are destined to become eggs and sperm and sexual organs, are a little rebellious—they travel all over the fetus, mostly traveling along the body’s center line. And they are more flexible than most cells, with more plasticity.

Dr. Joanna Gell with a patient

That combination of wandering and plasticity is a recipe for potential trouble: these cells can mutate into tumor cells, and they can lodge most anywhere in the body. When they lodge in the brain—the “intracranial” part of their name—it’s especially problematic, because of that tendency to wander along the center line of the body. They tend to grow deep in the center of the brain, near the pituitary and pineal glands, where they are hard to see and hard to get at. That matters because they come in two general varieties: germinomatous and non-germinomatous, with very different prognoses. Germinomatous tumors respond well to radiation and chemotherapy, and most children with them can be saved. But non-germinomatous tumors are far more dangerous. About half of children with these tumors do not survive. These tumors need much higher doses of radiation and much more intense chemotherapy. If the oncologist treating the child doesn’t know which kind of tumor it is, he or she cannot be sure of using the right treatment plan. If the oncologist assumes the child has a germinomatous tumor and is wrong, that child stands a good chance of not surviving. And wrongly assuming that the tumor is non-germinomatous would mean exposing the child to unnecessarily high doses of chemotherapy and radiation, with all the possible serious long-term side effects that represents.

Proceed with Caution

The only way to be sure what kind of tumor you’re dealing with is to do a biopsy. But again, these tumors tend to be deep in the brain, which means that the surgery needed to get a biopsy could damage surrounding healthy brain tissue and glands. That’s why most surgeons would prefer not to do that biopsy unless it’s absolutely necessary.

And this is where Dr. Gell’s research comes in. She’s working on new, non-invasive tools for identifying tumors. Specifically, she is looking at biomarkers that occur in cerebrospinal fluid. Biomarkers are proteins shed by a tumor and are distinctive to it. In the case of germ-cell tumors, we know of two biomarkers: One is a hormone produced by placentas after a fertilized egg implants itself. If that hormone shows up in a child who cannot be pregnant, it can indicate cancer. The second biomarker is similar: It is produced by a fetus’ yolk-sac or liver. Once the child is born, this production stops, so normally, it should only be present in very low levels. If it shows up in larger quantities, it could indicate a tumor.

Both of these biomarkers can be found in patients’ blood serum or cerebrospinal fluid. Collecting samples is relatively easy and decidedly safer than surgery. But each of the known biomarkers can be produced by either kind of germ-cell tumor. So we need more precise biomarkers, and that is what Dr. Gell is looking for. Her research so far suggests that microRNA may be one key. MicroRNA is a molecule that regulates gene expression, and it has proved very useful in several areas of medicine. The microRNA of each kind of tumor should be distinctive. The other potential tool is circulating tumor DNA. Tumors have DNA that is different from other kinds of cells, and some of that DNA is picked up in cerebrospinal fluid in the brain and circulates down the spine. Again, if she can identify the DNA specific to each type of germ-cell tumor, that should provide an easy, safe, specific way to come up with a diagnosis and appropriate treatment plan.

In order to be sure of the accuracy of the work, Dr. Gell needs a large number of samples, so she is working to establish a consortium of 20 pediatric hospitals to share samples. If she is successful, this will have a tremendous impact on the diagnosis and treatment of these deadly cancers and help save many children’s lives.

Covering What Insurance Doesn't

Pediatric cancer research receives very little government funding compared to adult cancers, and medical insurance doesn’t cover research, so Dr. Gell’s work relies on donor support. One philanthropist who has taken a special interest in Dr. Gell’s research is Bob Shanfield, an investment expert with Ares Management Corporation. “Having the opportunity to meet with Dr. Gell and hear about her work is inspiring,” said Bob. “I’m so proud to support her work and I hope more people partner with Connecticut Children’s physicians to chart the future of medicine.”

Dr. Gell is also a recent recipient of the prestigious Young Investigator Award from Curesearch for Childhood Cancer. This grant award supports her work that focuses on identifying a more effective and less toxic therapy for intracranial GCTs (iGCTs). Current treatments result in significant morbidity including renal impairment, secondary malignancies, cognitive impairment, visual-field impairment and endocrine disorders. If proven, the targeted therapy has the potential to not only improve the iGCT survival rate significantly, but may also benefit a broad range of patients.

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