by St. Baldrick's Foundation
July 20, 2020

With a long history of support from the St. Baldrick’s Foundation, Dr. Eric Raabe of Johns Hopkins University is a “Rockstar Researcher” in pediatric brain tumors.

As an undergraduate student, Dr. Raabe volunteered at a children’s hospital where a pivotal moment influenced his decision to become a pediatric oncologist. He vividly remembers a young boy who had relapsed and was being hospitalized after having one of his lymph nodes biopsied. The boy sat alone in his room with the shades down. In the dark room the boy became more and more withdrawn as he sat and waited for the results. He thought he was going to die.

No sooner had the results come back negative for recurrence of his cancer, than the blinds went up and he wanted a pizza with everything on it. The experience left a lasting impression and prompted Dr. Raabe’s decision to become a pediatric physician scientist. In that moment he realized the impact he could make in a scared and sick child’s life. He decided then and there that he wanted to be part of providing a path to hope and a path to a cure. He wanted to help guide these children from the darkness to a place of hope and light.

doctor in mask

Mentored By A Legend In Pediatric Oncology Research

During the course of interviewing for med school, Dr. Raabe met Dr. Robert Arceci, a cancer research pioneer and thought leader in pediatric oncology research who also served as chair of the St. Baldrick’s Scientific Advisory Committee. After Dr. Arceci’s tragic death in 2015, the St. Baldrick’s Foundation created a unique award in his memory to spur innovative research. Dr. Raabe was fortunate enough to work alongside Dr. Arceci in his lab while doing his PhD and was mentored by him for many years.

In fact, he still hears the legendary doctor’s voice in his head guiding him in the great work that he’s doing. Dr. Raabe described how when patients weren’t doing well, Dr. Arceci would say, “We have to get smarter about this. We have to get in the lab and find out why it’s not working out.” The word “why” is an important question that drives researchers like Dr. Raabe. As he describes it, “Our patients are also our why. They are the motivation for why we spend so many hours in the lab.”

Research Started By A St. Baldrick’s Fellow And Scholar Now Propels Progress

Dr. Raabe was a St. Baldrick’s Fellow from 2008 to 2011 and a St. Baldrick’s Scholar from 2011 through 2016. To say that this investment in his training and early work was important is an understatement. As Dr. Raabe put it, “Funding from St. Baldrick’s was critical and continues to be critical for helping the next generation of pediatric cancer researchers.”

These grants allowed him to make that all important transition from being a fellow to setting up his own lab and starting research projects that even now, many years later, are continuing to bear fruit. The research Dr. Raabe started as a St. Baldrick’s Fellow and Scholar will continue to propel advancements in research over the next decade. As he put it, “The commitment and investment from St. Baldrick’s provides the time needed to develop research that may take several years to get going. But when it pays off, it pays a dividend for 10 years and has a long-term trajectory.”

Researching Medulloblastoma: An Aggressive And Rare Form Of Pediatric Brain Cancer

Medulloblastoma is the most common malignant brain tumor in children. Despite being one of the most high-risk pediatric brain cancers, oncologists have discovered very few new drugs for this disease in the past 30 years and currently there are very few long-term survivors. But Dr. Raabe is working hard to change that.

No matter the patient or what cells looked like under the microscope, medulloblastoma was once thought to be the same disease. We now know there are actually subgroups and patients with subtypes don’t tend to do as well as others. So, treatments have begun to be subgroup specific as opposed to a “one size fits all” model. As part of this streamlined approach, researchers like Dr. Raabe now explore more targeted therapeutic approaches for these subtypes, outside of surgery, radiation and chemotherapy.

First St. Baldrick’s Funded Research Project

A more targeted approach that Dr. Raabe has explored includes utilizing small molecule inhibitors to target a particularly aggressive subtype. This subtype, Group 3 medulloblastoma, makes up 28% of cases and results in the most relapses in patients and has a survival rate of only 30-40%.

To address this aggressive subtype, Dr. Raabe and his team created a computer-based method called Disease-model Signature vs. Compound-Variety Enriched Response (DiSCoVER). This allowed them to use drug sensitivity databases to identify drugs that might be effective against medulloblastoma. Using CDK inhibitors they decreased medulloblastoma growth by more than 50% and more than tripled cell death compared to untreated cells.

“Results of the new treatment are very promising for Group3 medulloblastoma,” said Dr. Raabe. The Children’s Oncology Group (COG) is currently considering CDK inhibitors in a clinical trial being planned for these high-risk patients with relapsed medulloblastoma. Dr. Raabe is hopeful that the application of this finding will soon make its way to pediatric patients.

Second St. Baldrick’s Funded Research Project

Another of Dr. Raabe’s studies focused on the abnormal cancer cell and metabolism. The insight was that cancer cells use energy differently than normal cells and that’s a vulnerability that could be exploited. Their study sought to identify drugs that could alter the metabolism of medulloblastoma cancer cells. Dr. Raabe and his team believe there’s a “therapeutic index” which means that the worst type of medulloblastoma cancer cells are more sensitive to these drugs than normal cells. This is just another example of a St Baldrick’s funded project that has made it into publication and subsequently has a good chance of being applied to pediatric patients soon. Dr. Raabe and his team have leveraged St. Baldrick’s funding to apply for and receive NIH R01 funding for their on-going efforts to find metabolic therapies for high-risk medulloblastoma.

Staying Motivated: Even Though There Are So few Long-Term Survivors

In general, medulloblastoma has a 70 to 80% survival rate. However, Dr. Raabe’s research focuses on a high-risk subgroup of medulloblastoma with only a 30-40% survival rate. And there are very few long-term survivors. You might think staying motivated could be an occupational hazard. Especially when trials can last 10 years and you may only have 20 to 30 years before you retire. When asked what keeps him motivated, it turns out that what prompted Dr. Raabe to choose pediatric oncology research – providing a path to hope and a path to cure – is still what keeps him motivated. The published papers and grants provide encouragement but in the end they’re just a means to an end. What drives him is getting the right drugs into clinical trials for patients so they can eventually be applied and become part of the treatments that really make a difference.

So, on the days that he gets frustrated he looks to his bookshelf for inspiration. On it sits thank you letters from patients, memorial cards from patients’ funerals he’s attended, works of art from patients no longer with us and a drawing from a girl named Hannah. It was the “Hannah’s Heroes” Hero Fund which funded Dr. Raabe’s Scholar grant. Looking at all of them helps Dr. Raabe get perspective. It helps him realize what it’s really all about — helping patients do better.

drawing from patient

Continuing To Fund Brain Tumor Research: A No Brainer

Pediatric brain tumors are the number one cause of pediatric cancer mortality and they haven’t seen the type of progress other types of pediatric cancer have. So, the need to support funding to identify and validate new drugs and treatments for patients is critical. St. Baldrick’s has funded a great deal of brain tumor research that’s paying dividends. But it’s something we need to continue to focus on. As Dr. Raabe said, “St. Baldrick’s has played a critical role in helping me to help patients and has been a great source of funding not only for me but for many of our other faculty here at Johns Hopkins. What you are doing is so important for helping our faculty, junior faculty and patients so thank you.”

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