Childhood Cancer

Brain Tumors

Brain tumors can be low-grade, which tend to grow more slowly, or high-grade with faster growth rates and more commonly spread into normal brain tissue. There are several rare types and sub-types of pediatric brain tumors.  

Make an Impact on Brain Tumors - Donate now!

Latest Brain Tumors grants

Pamela Wolters, PhD, Principal Investigator
National Cancer Institute
Psychosocial Family Impact Grant, Awarded 2017
Susann Brady-Kalnay, PhD & Efstathios Karathanasis, PhD, Principal Investigator
Case Western Reserve University
Innovation Grants, Awarded 2017
Ranjit S. Bindra, MD/PhD & Mark Saltzman, PhD , Principal Investigator
Yale School of Medicine
Innovation Grants, Awarded 2017

Latest Brain Tumors blog posts

July 9, 2018

by Trish Adkins

In 2000, the first draft of the map of human genome—a mosaic representation of characteristics of what makes our biology uniquely human—was released. The map paved the way for more genomics research in several fields ranging from human biology to agriculture and gave scientists models of genetically normal cells which they could compare to abnormal cells, like those cells that make childhood cancer so deadly.

Now, in 2018, an ALSF funded-research project has resulted in the release of over 270 genetic sequences of 25 different types of childhood cancer used routinely by the National Cancer Institute’s Pediatric Preclinical Testing Consortium (PPTC). Each unique tumor model and its biological characteristic data is available to all academically qualified petitioners—opening the door for breakthroughs in childhood cancer research.

Keep reading to learn how cures are getting closer, one childhood cancer genome at a time. 

The story behind the 270 models begins with the PPTC

Founded in 2015 and funded by the National Cancer Institute, the consortium works to develop reliable preclinical testing data for potential pediatric cancer drugs. There are hundreds, maybe thousands of potential cancer drugs—making the study of each drug in a pediatric clinical trial impossible. The PPTC narrows down the list, providing researchers with reliable drug effectiveness data that they can use to accelerate research from “bench to bedside;” bringing science out of the lab and into the clinic. The models studied are directly derived from childhood cancers at diagnosis or relapse, and thus are directly representative of the types of cancers treated in clinical trials.

However, while there is a large pool of potential drugs, there was not a large pool of accurate pediatric tumor models for which to test the drugs. This has long been a struggle for the pediatric oncology research community. Over 14.1 million people are diagnosed with cancer each year worldwide, but only 250,000 of those cases are pediatric cancer. The pool of potential tumors to model is small and obtaining viable tumor cells is difficult, especially for some types of pediatric cancers like spinal cord tumors where securing tissue samples is tricky because of the tumor’s location. 

The PPTC had an idea for a new major effort, the Pediatric Preclinical Genomic Characterization Project, which sought to characterize the tumor samples being used in drug testing. These patient-derived xenograft (PDX) childhood cancer models were being used routinely, but the majority did not have detailed genetic data available. 

The potential was enormous: with a critical mass of PDX models made available to the scientific community, the PPTC could accelerate the route to clinical trials much more rapidly than ever before, bringing potentially lifesaving treatment to children waiting desperately for cures.

There was one catch: there was no funding available for a PDX sequencing project. That’s when ALSF entered the picture. 

The Foundation learned about the PPTC and its desire to generate high-quality PDX genetic data to streamline science’s understanding of why novel treatments work in some cases, but do not work in others, and immediately recognized its promise. 

“ALSF has a legacy of filling critical research and family services gaps in the childhood cancer community,” said Liz Scott, Co-Executive Director of ALSF.  “We knew that funding the PPTC’s genomic sequencing project had the potential to spark long-lasting impact, collaborative efforts and ultimately advance the pace of finding cures for all kids with cancer.”

Legacies of Hope
With the ALSF funding, the PPTC could characterize the stored samples that had been donated by children battling pediatric cancer. Some donations came while a child was in treatment, with an institution’s requested permission to use extra tumor tissue that was not needed for diagnosis or treatment protocol, for research.  

Other donations came from families eager to find cures even when it was too late for their own child. These profound gifts, given at the time of death, left behind a legacy of hope waiting to be unlocked.  

The PPTC has access to over 400 samples representing 25 different types of childhood cancer, stored at -80℃ in its five locations at institutions in the United States and also in Australia, and continues to generate more, often in collaboration with Dr. Patrick Reynolds who receives ALSF funding for the Childhood Cancer Repository where many genetic models are generated. The vast majority of the samples represent relapsed disease and have the promise of modeling childhood cancers at the time that many new investigational treatments are tried in the clinic in Phase 1 trials.

While the PPTC could have tried to establish the tumor lines in a test tube or dish, the researchers leading the project knew from prior experience that growing tumors in artificial environments could lead to the generation of different mutations in revolt to their new homes. These mutations would lead to inauthentic cell lines and muddy the search for drugs that could work. 


Accelerating the Clinical Trial Process
Bringing the right drugs to the clinic has long been a struggle for pediatric oncology researchers.  

The first priority is to ensure a patient’s safety in a clinical trial by adhering to specific safeguards before the trial begins and during the trial. But a safe drug is not necessarily effective and can offer false hope to patients who are enrolled in clinical trials after one relapse—or several.  

Using the PDX models, researchers could discover the “good drugs”—the drugs most likely to be safe and effective in killing cancer cells, and also discover the “bad drugs”—those that are not effective and those that might even result in resistant disease.

The models also give researchers the opportunity to continue to move away from treating diseases by name and begin treating the specific genetic lesions that might drive cancer growth. It is the literal meaning of “killing two birds with one stone”— two different types of cancers may share a genetic trait and in turn, could be sensitive to the same drug. 

“With good models, we can begin designing experiments more robustly and begin getting the right drugs to the clinic and to children quickly,” said Dr. John Maris, MD, of ALSF’s Scientific Advisory Board and Children’s Hospital of Philadelphia’s neuroblastoma representative in the PPTC.

ALSF’s contribution allowed the PPTC, in collaboration with Baylor College of Medicine and Nationwide Children’s Hospital (led by David Wheeler and Julie Gastier-Foster), to genomically characterize over 270 PDX models with four different genomic tools—each tool giving researchers more clues to how the genes and proteins drive cancer growth.

Researchers worked to filter out any noise or irregularities in the final data, using existing cancer cell knowledge and past research. They have ensured the models matched their cells of origin and have retained known cancer driver mutations over time. 

The PPTC began using the data immediately—fulfilling its mission of matching drugs to genetic targets and testing in advance of human clinical trials. 

Now, eighteen months after the PPTC commenced the PDX project, other scientists now have the same opportunity. The data, which was released on July 9, 2018, is available to all academically qualified petitioners through the PedcBioPortal for Childhood Cancer Genomics (pedcBio portal). Raw characterization data will be available on the database of Genotypes and Phenotypes (dbGaP) in the coming months. Tissue samples will be available by request—for just the cost of postage to ship. 

“When childhood cancer relapses, it can become lethal,” said Dr. Maris. “But today, the scientific community has open access to deep genetic profiling that will help overcome some of the major problems we have when treating childhood cancer. We’ve now accelerated years ahead in our search for cures.”

Read more about the PPTC project, as well as other innovative ALSF research here. 

March 16, 2018

 

by Trish Adkins, ALSF

Dr. Jean Mulcahy-Levy, of the University of Colorado Denver got her start in research studying the behavior of fruit bats at the zoo.  

Now, she’s using Nobel Prize-winning science to find cures for brain tumors. 

Dr. Mulcahy-Levy’s research focuses on how blocking a cellular process called autophagy could eliminate brains tumors that have a specific mutation. All cells—both normal and cancer cells—perform autophagy, which is basically a cell-recycling program. Cells convert proteins within themselves into new energy. In 2016, a scientist named Yoshinori Ohsumi discovered the mechanisms that make autophagy happen and won the Nobel Prize in Physiology. 

Now in 2018, Dr. Mulcahy-Levy’s application of his work is leading to a potential clinical trial for children battling relapsed brain tumors. We spoke with Dr. Mulcahy-Levy about her research career. 

Who encouraged you to follow your passion for science and research?

(JL) When I was applying to college, I toured a couple of places. But it was when I met Dr. Becky Houck at the University of Portland that I knew I had found my science home. Her openness, passion and excitement for science was infectious, you just had to enjoy biology when you were around her. I was lucky enough to get my first taste of scientific research with Dr. Houck, studying the behavior of fruit bats at the zoo (funny question we tried to answer- did fruit bats have a preference for the right or left hand?) and how a summer camp education program changed kids’ perceptions of bats (changing kids view from vampire bat to cuddly cute fruit eating animals). 

Dr. Houck’s excitement for her work, and her constant support of my goals of being in science, were exactly what I needed to commit myself to a future in science. I have come a long way from trying to keep track of fruit bats and convincing kids the bats won’t eat them. But from that small project and the mentorship of my first strong female example of a scientist, I’ve never looked back.
 
What are obstacles that you have faced?

(JL) I think as a woman (or really anyone) in science you have to have the support of everyone around you to be successful. I have been lucky in that I haven’t had many obstacles to overcome and I have never felt that anyone thought I was inferior because I was a woman. 

I have had support from my female teachers and mentors such as Dr. Houck. But I have also been fully supported by the male teachers and mentors in my past. Dr. David Alexander, my pre-med advisor in college supported every way I tried to manipulate my schedule to get exactly the classes I needed to be ready for my medical training. He was also married to an intelligent and successful scientist in her own right, Dr. Paula Tower, and together they helped me get my first lab research job. From there, I have sought out the best research mentorships and training I could get.
  
How did Dr. Alexander and Dr. Tower’s support help you as a student?

(JL) I would never be where I am now without my pre-med advisor Dr. Alexander (affectionately known as Dr. A) and his wife Dr. Tower. College is a hard time and trying to get started in science is hard. But they constantly modeled not only excitement and joy in science but also the importance of home and family. Watching the two of them gave me a picture of what I wanted my life to be in the future. Dr. A passed away from colon cancer in 2013. But before then, he and Paula were my go to people to keep me sane during college, medical school, residency and fellowship. Paula continues to help me through the struggles of starting my own lab, training research assistants, how not to get annoyed at grant or manuscript reviews, and how I should really learn to cook (but that her house is always open if I need a good home cooked meal).

How has your family supported your career?

(JL) It has been traditional in the past that a wife will follow her husband for work. But my husband recognized early on that in order for me to succeed in research, I needed the freedom to go where the best training and opportunities were. He told me early in our relationship that he supports me and whatever I need to be successful. He has rearranged his life and the life of our son to give me the flexibility to surround myself with the best research environment. I could not have gotten to where I am without his selfless encouragement, willingness to pick up his life and move, and to sit there and listen to me drone on about some lab thing that is going great (or not so great) without falling asleep!

When you were 10 years old, what did you want to be when you grew up?

(JL) A doctor. I was always going to be a doctor. I never did have a back-up plan, so thank goodness this is working out!

If cancer was cured, what would you be doing?

(JL) In my secret other life, I “work” in my husband’s motorcycle dealership and I am an officially licensed used car and motorcycle salesperson. So if cancer were cured, I would likely be spending my days working with my husband and playing with motorcycles!

In honor of Women’s History month in March, ALSF will feature interviews with some of our outstanding funded women researchers on the ALSF blog. You can follow along here

March 9, 2018

by Trish Adkins, ALSF

Ever since she was a child, Dr. Catherine Flores, of the University of Florida, loved the challenge of experimenting and investigating the origins of things. Now, as a pediatric cancer researcher, Dr. Flores is applying those interests to curing childhood brain cancer. 

ALSF awarded Dr. Flores a Young Investigator grant in 2015, which she used to study the preclinical development of adoptive cell therapy to fight high-grade gliomas,  a category of fast-growing pediatric brain tumors with particularly poor survival rates. Her project laid the groundwork to better understand how a child’s own immune system cells could be altered to fight brain tumor cells. This research may lead to better survival rates and minimize the use of treatments with high levels of toxicity. 

Her work also led to a phase 1 clinical trial that studies the use of immunotherapy in kids with high-grade gliomas. The study is set to open in March 2018 and phase 1 will determine safety and dose. It is the first immunotherapy study of its kind for children, moving the oncology world one step closer to a breakthrough and a cure. 

We spoke with Catherine Flores about her work and what it is like to be a woman researcher. 

What made you want to get into science and research? 

(CF): I have always been a curious person. I love exploration and experimentation. I love the discovery. I find "failed experiments" to be a challenge, not a discouragement. I never really realized that there aren't many women in science until my first faculty appointment and I am one of only two tenure-track female faculty members in my department. 

What are obstacles that you have faced?

(CF): I have a two-year-old and balancing life is such a challenge. Being a researcher is not a 9-5 job, so rearranging the day and writing at night to get it all done was and is a huge obstacle. But I love it all. It is just challenging, that's all. 

Sometimes, I feel a little judged when I come to work covered in banana, or can't do 6 pm meetings. BUT, I do a huge amount of work between my daughter's bedtime and sunrise. 
    
If cancer was cured, what would you be doing?

(CF): When I was 10 years old, I wanted to be a marine biologist. I love the ocean and its animals. It is still fascinating. After I cure brain cancer, I still want to be a marine biologist. 

Who are your role models?

(CF): Working moms with multiple children and Michelle Obama. 

Do you have an impact story from your research—a story when you saw your work help children?

(CF): We have a clinical trial out of our program for children with recurrent medulloblastoma and PNETs. One of our patients, Sawyer, had always wanted to be a scientist. So I closed down the lab for the day and set it up to make it "Sawyer's lab". We had a personalized lab coat made for him with the University of Florida and his name all embroidered. We set up a kid-friendly experiment for him on each bench complete with exploding bottles, dry ice, glow in the dark chemistry, all the kid things! At each bench, I had a different grad student helping him - because grad students in lab coats are super cool to an 8-year-old boy. Then we all had pizza which is his favorite. His mom mentioned that Sawyer had said it was more fun than Disneyland. 

Sadly, Sawyer passed away the following Christmas. Even though we couldn't ultimately help him fight against his disease, we at least let him be a scientist for a day. Sawyer was already unstable on his feet from his cancer, so his dad was there to keep him steady. That family made an impact on our grad students and researchers because we were all touched by him and inspired and motivated to do more. As lab researchers, we generally don't come in contact with patients, but it was amazing to see who we are trying to help. Interacting with him during a fun time made me want to work even harder. It also made me realize that receiving grants and manuscripts (our metrics as academics) are great, but they are nothing compared to actually finding a cure. 

This picture of me (above) with Sawyer making magnetic slime, is my favorite. It hangs in my office to inspire me every day. 

In honor of Women’s History month in March, ALSF will feature interviews with some of our outstanding funded women researchers on the ALSF blog. You can follow along here.