Childhood Cancer

Diffuse Intrinsic Pontine Glioma (DIPG)

Diffuse Intrinsic Pontine Glioma (DIPG) is a rare tumor of the brainstem that occurs almost exclusively in children. The tumor appears in the delicate area of the brainstem, called the pons, which control critical body functions like breathing and blood pressure. The tumors infiltrate healthy brain tissue, causing severe symptoms. 

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Latest Diffuse Intrinsic Pontine Glioma (DIPG) grants

Michelle Monje, MD, PhD, Principal Investigator
Stanford University
'A' Award Grants, Awarded 2011
Mark Souweidane, MD & Richard Ting, PhD, Principal Investigator
Weill Cornell Medical College
Innovation Grants, Awarded 2016
Mario Suva, MD/PhD, Principal Investigator
Massachusetts General Hospital
Innovation Grants, Awarded 2016

Diffuse Intrinsic Pontine Glioma (DIPG) Heroes

Latest Diffuse Intrinsic Pontine Glioma (DIPG) blog posts

July 18, 2018

by Trish Adkins

When a child receives the diagnosis of diffuse intrinsic pontine glioma (DIPG), the diagnosis comes with an end date. 

Thus far, DIPG is always lethal. 

But, ALSF-funded grantee Dr. Michelle Monje of Stanford University, does not believe it has to be. Dr. Monje, who specializes in studying high-grade gliomas, is close to a powerful breakthrough that could change the prognosis for children with DIPG.

“The amount of progress that has been made in the study of childhood gliomas in the past five years is more than has been made in the last 50 [years]. It is a really exciting moment of progress and hope,” said Dr. Monje. 

Dr. Monje recently demonstrated that a certain type of CAR T Cell immunotherapy killed DIPG cells in murine models. CAR T Cell immunotherapy has been approved to treat certain types of pediatric leukemia and has proven effective in clinical trials for other types of the childhood cancer. In Dr. Monje’s lab, these engineered immune cells were given intravenously and then went directly to work clearing the tumor cells in the brain. The result: instead of seeing tens of thousands of DIPG cells, only a few remained. 

The next step: human clinical trials that could offer real hope to children battling DIPG. 

We interviewed Dr. Monje about her research, her inspiration and her experience as a woman in science. 

ALSF: Did you always want to be a doctor?

MM:  I have wanted to be a doctor since kindergarten, inspired by the father of my best friend who was a pediatric hematologist/oncologist. I remember my mother telling me, “He takes care of sick children. It is the most important job that anyone can do.” This dream was nearly derailed in high school because of a discouraging moment in my biology class when a teacher once said to me, “it’s a rare woman who has a mind for science, sweetheart.” But, I got back on track because of a wonderful biology professor (Kate Susman) in college (Vassar). 
ALSF: What challenges have you faced in your career?

MM: I have had enormous support from my family and from mentors at all stages of my training from college to the present day. I am enormously lucky and not all women in science have had that kind of support. But there have been challenges. 
I do find that, throughout my career, it has been a struggle at times to be taken seriously, to finish my sentences without interruption, to have my points heard. While these moments are less frequent now that I am more senior, can point to more accomplishments and have a few grey hairs, it definitely still happens. I have four children, and during each pregnancy I noticed a prominent uptick in moments I did not feel I was perhaps taken as seriously as my male colleagues.  
ALSF: How do you juggle the demands of parenthood and your amazing work in the lab? 

MM: Having four children during my clinical training, postdoctoral fellowship and early faculty career was not easy, but it was absolutely do-able. I make this point because as a young trainee, many people gave me the (unsolicited) advice that one cannot have a big career in medicine or science and also have children. That at some point, I would have to choose between motherhood and science.

I ignored that advice and it has all worked out so far. It worked out, in part, because I asked for what I needed (time to pump milk at work, access to a lactation space with a door and a power outlet that was not a public restroom, meeting times that did not conflict with daycare pick-ups) and did what was a little bit taboo (routinely traveling with my nursing baby and my mother as a caregiver, while my husband was home with the other kids, when I attended conferences or scientific meetings, once giving a talk with an infant sleeping in the baby carrier strapped to my torso.) It worked out for me because I was allowed to bend and break the rules. What I would like to now advocate for is a system in which the rules are designed to support scientists and doctors during pregnancy, lactation, and parenthood. Young scientists and doctors who are new parents are busy enough without needing to figure out the basic logistics necessary to get through each day. 
ALSF: What would you do if cancer was cured?

MM: If cancer was cured, and the neurological side effects of cancer therapy were also cured, I would happily focus my research entirely on the basic neurobiology of how the brain develops and how it adapts throughout life. I am endlessly fascinated by the nervous system. And I would happily administer those cures to soon-to-be healthy children in the clinic. 

Dr. Monje’s work studying DIPG was recently published in the journal Nature Medicine. Read more about her work studying high-grade spinal cord tumors, here. 

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.