Collaborative Corner

Q&A with CBTTC Scientific Co-Chair, Dr. Javad Nazarian: Addressing Challenges in DIPG Research

Diffuse Intrinsic Pontine Glioma (DIPG) brain stem tumors are among the most deadly form of pediatric cancer, affecting approximately 200-400 children in the US each year.  While a diagnosis of DIPG is fairly rare, there is no known cure, and a 5-year survival rate of less than 1%. On average, DIPGs become fatal about 9 months post-diagnosis.

Uncovering treatments and cures for DIPG brain tumors are one of the greatest challenges facing pediatric cancer researchers in the US and across the world.  However, the number of scientists choosing to concentrate their research efforts on this disease has risen steadily over the past decade, as has the ability for research collaborations across institutions and international borders to accelerate progress in studying and ultimately curing DIPGs in children.

We recently spoke with Dr. Javad Nazarian, PhD, MSC of Children’s National Health System; Scientific Co-Chair of the Children’s Brain Tumor Tissue Consortium (CBTTC), Primary Investigator at the Pacific Pediatric Neuro-Oncology Consortium (PNOC), and a leading expert on DIPG research; to get his perspective on the current challenges and promising developments in the global effort to eradicate DIPG tumors.

 


Dr. Nazarian, why did you choose to focus on DIPG in your research, and how long have you been studying this type of pediatric brain cancer?

I was approached by Dr. Tobey MacDonald, Director and Aflac Chair of the Pediatric Neuro-Oncology Program at Children’s Healthcare of Atlanta, to see whether we could study DIPG given the limited numbers of tissues specimens that were available for this type of pediatric brain tumor at the time.  

This was 2008, and I had not heard about DIPG. In fact, if you do a literature search, you will notice that there were only a handful of scientific papers published on the biology of DIPG up to that year.  Essentially, we didn’t know much about the biology of the disease.  

Dr. MacDonald reached out to me because a DIPG patient’s father wanted to change the status quo. The field has changed greatly since then, and we have learned so much; specifically because of parents’ persuasion and them not accepting what we have to offer them in the clinic. 


What, historically, have been the most challenging aspects of this disease that researchers have grappled with?

DIPG cancers occur in a highly sensitive and vital neuroanatomical brain section.  This makes them surgically inoperable. Moreover, drug delivery to these tumors is often blocked by the protective membrane called the blood-brain barrier (BBB).  

Lack of surgery has been the main reason for delayed understanding of disease biology.  And now that we know some of the molecular drivers of the disease, drug deliver has become a challenge.  For the most part, we do not know whether therapeutic drugs cross the BBB. And if they do cross, we’re uncertain to what degree and for how long the drug’s effects will persist.  

At this point in time, clinicians still have not identified effective drugs to treat DIPGs, and are also limited to how existing drugs can be combined and administered safely to patients.  

In my opinion, we need to first focus on answering these questions in preclinical settings and/or build next generation clinical trials that could answer some of these fundamental questions. 


Are there any new developments in DIPG research/treatment that you find most promising?

Unfortunately, we have not made a dent in this devastating disease.  But everyone is working hard to make the first crack at this tumor.  

Families have done a fantastic job in raising awareness and more researchers are now joining the field of DIPG research. There are also international collaborations that are forming both at clinical and preclinical levels. The CBTTC has done phenomenal work in driving some of these initiatives, such as the expansion of correlative studies within clinical trials including efforts by the Pacific Pediatric Neuro-Oncology Consortium (PNOC). 


Project OpenDIPG is an exciting recent partnership between the CBTTC and PNOC, led by yourself and Dr. Adam Resnick, PhD of Children’s Hospital of Philadelphia.  What will the OpenDIPG project enable clinicians and researchers to do, and how will it make an impact on DIPG research?

Data is everything for researchers and clinicians. One cannot design effective therapies without knowing what constitutes and what drives the tumor. Project OpenDIPG aims to bring all data together under one umbrella where they can be easily accessed and used.  

The project is collating and releasing newly-generated, DIPG-omic and clinical data, including liquid profiling of cerebrospinal fluid (CSF) and plasma, DNA methylation, copy-number variation (CNV), proteomics, whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA-seq from individual investigator labs and consortia efforts on a rapid, pre-embargo release cycle. To date, 460 clinical research subjects have been enrolled with corresponding biospecimens collected and 5,070 files of data generated.

DIPG does not discriminate borders, race, or gender.  Thus, fragmented data will only slow down progress. OpenDIPG will help to build a one stop shop for data access…free and for all.

 

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