2014 Pediatric Cancer Nanocourse – Stanford University
MCF Board Member
In early August I got to spend a week roaming the campus of my dream school…Stanford University. Although I have long held Stanford in high esteem, my perspective became much more personal when, back in 2011, McKenna was diagnosed with DIPG. It was during that time that I first learned of Dr. Michelle Monje, a well respected pediatric brain cancer researcher and Assistant Professor of Neurology at Stanford. Only six months after Macky’s diagnosis, there was a heartbreaking reason to work directly with Dr. Monje…to help coordinate the Wetzel family’s generous, yet incredibly painful, decision to donate Macky’s tumor tissue to Dr. Monje’s lab at Stanford for further research. This was how I became personally aware of Dr. Monje’s profound compassion for her patients and their families as well as her ground breaking and innovative research aimed at finding a cure for pediatric brain cancer.
An informal part of Dr. Monje’s work involves partnering with and updating the private foundations that help to fund research conducted by her lab, as well as, that of other renowned researchers and institutions all over the world. To that end, Dr. Monje and Stanford graciously agreed to host the 2014 Pediatric Cancer Nanocourse in order to educate pediatric brain cancer advocates on the current science and research developments in DIPG pathobiology, diagnosis and treatment as well provide opportunities to strengthen the relationships between foundations and researchers as we work together for a cure. A “nanocourse” is basically just a fancy word for “crash course” which is a very accurate description of my week at Stanford!
For five days we listened as leading doctors and researcher’s presented on a myriad of topics related to pediatric brain cancer…from it’s theorized origin, to current research findings and developing clinical trials, to treatment standards of care, as well as (the devastating) late term effects of treatment on long term survivors. While I couldn’t possibly summarize all that we learned here in this post, here are my Top Ten important take-aways from the week…
1. Brain Tumor Tissue Donation is Critical
Although the total number of brain tumor tissue donations is still fairly small, such donations have played a critical role in developing new and novel approaches to pediatric brain cancer treatment. In fact, the propagation of these tumor cell lines over the past three years has led to more advancements in the area of DIPG research than in the last thirty years combined! With that said, at present only ~25% of tumor tissue harvested will be successfully cultured allowing for the propagation of cell lines. Dr. Monje and other researchers have learned a great deal in a short period of time about the factors that increase or decrease the potential for creating a successful cell line from tissue donation and are working hard to ensure that every donation can become a durable cell culture.
2. With DIPG Tumor Tissue Donation Increasing, There is More Hope for Developing Clinical Trials for Effective Treatment
Clinical Trials are the process by which drugs or other treatment interventions are tested for safety and efficacy. They are divided into four classes:
Phase I: A new drug or treatment is tested in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. The actual efficacy of the drug is not tested in the phase.
Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use.
There has never been a Phase III or IV DIPG clinical trial in the United States. In other words, there has NEVER been a drug developed that shows any efficacy in the treatment of DIPG.
Historically, DIPG and other brain stem tumors are some of the most difficult of all brain cancers to treat. With the recent availability of tumor tissue for research there is finally real hope for accelerating the clinical trial process and therefore the development of treatments that can effectively target these tumors.
3. Tumor Cell Lines Have Already Led to Breakthrough Research
The breakthrough availability of tumor cell lines has enabled researchers to test these cancers against a panel of 60 known chemotherapy agents to look for patterns of efficacy and develop strategies for creating clinical trials that test new combinations of chemotherapy drugs to attack these tumors with greater success. As a result of this work, clinical trials are already in process for testing these theories and creating hope on the horizon.
4. The Study of Epigenetics Is Crucial to Understanding DIPG
Epigenetic research (the study of how gene expression is controlled within a cell) has led to the breakthrough identification of certain histone and other mutations that are present in pediatric high grade gliomas. Further research is looking at how these mutations operate within DIPG tumors and at identifying the cell of origin for DIPG tumors. Once determined, this information can be used to develop therapeutic strategies for treating DIPG.
5. Research Labs Require a Variety of Forms of Financial Support
“Indirect costs” are like a “tax” that the research lab must pay to the University in order to accept the grant funds. The Universities at which the research is being conducted will charge the researcher a percentage of the total grant funds to cover the “indirect costs” of performing the research (like keeping the lights on and other lab infrastructure services that the University provides), so if the granting Foundation does not cover these “indirect costs” then the researcher must pay these charges from other sources. If they cannot find other funds to cover the indirect costs, they cannot afford to accept the grant. For this reason, “indirect costs” are ideally built into the grant research budget… disallowing “indirect costs” penalizes the researcher for doing the work of that grant.
In the last three years, the McKenna Claire Foundation has donated nearly $410,000 to the Monje Lab, which not only provides “unrestricted funds” for DIPG research (funds Dr. Monje has flexibility in determining exactly how to allocate), but in addition, specific grants to cover a variety of administrative costs that support her research…from the salary of a research assistant whose primary responsibility is to administer the maintenance and distribution of the cell lines propagated by the Monje Lab, to costs associated with cell line shipping, to the costs associated with new tissue harvest. By covering these “non research”, administrative, costs the McKenna Claire Foundation is helping to ensure that the cell lines created from donated tumor tissue will not only be studied at Stanford, but at leading institutions all over the world. Already, McKenna’s tumor cell line has been distributed to more than 3 dozen researchers in countries as far as Australia, France and Spain The more researchers who work with these lines the faster we can advance progress!
6. Funding the Technology to Conduct Research is Just as Important as the Research Itself
Similarly, it is often difficult for researchers to obtain grant funding for “capital expenditures” e.g. one time expenses related to the purchase of equipment. The McKenna Claire Foundation has helped address this funding shortage by providing a grant for the purchase of cutting edge technology that allows creating “slices” of cultured mouse brain, thereby keeping the tumor microenvironment intact to study in a dish.
7. Creative Ideas are Necessary to Close “The Valley of Death”
One in five pediatric patients do not survive childhood cancer and these patients have had the same chance of survival for over 40 years. Because drug development is fueled widely based on market forces, science has outpaced treatment development, particularly for children. A gap between basic science and the development of clinical trials, known as the “preclinical gap” or “the valley of death” too often prevents new drugs for promising targets from reaching children. Creative and innovative approaches by “outside the box” thinkers like Dr. Charles Keller of the Children’s Cancer Therapy Development Institute) and Nancy Goodman, author of the “Creating Hope Act”, are critical to bridge this gap and bring drugs developed specifically for children to trial and market faster.
8. Advocacy for “Care” is as Necessary as “Cure”
Although the ultimate goal is to find a cure for pediatric brain cancer, we at the McKenna Claire Foundation understand this quest is a marathon, not a sprint, and “baby steps” are an important part of the journey. One of the ways pediatric brain cancer families and foundations can assist in this process is to continue to inquire and advocate for the development of better palliative treatment options for inoperable, terminal brain tumors. The 2014 Nanocourse participants have committed to following up on promising early clinical trials that present alternatives to the standard treatment of administering dexamethasone to alleviate the symptoms of brain tumor growth and the swelling caused by surgical intervention or radiation therapy. These alternatives aim to provide the same benefits of dexamethasone without the devastating side effects so many pediatric brain tumor patients must endure.
9. The Late Term Effects of Pediatric Cancer Treatment are Devastating
The late effects of cancer treatment on pediatric cancer patients are quite simply, devastating. Although patients diagnosed with DIPG do not currently survive long enough to fully experience these effects, as treatments are developed, it is a problem the DIPG community hopes to face one day soon. About 1 in 250 adults is a childhood cancer survivor, and of those, 65% of them survived a brain or other central nervous system (CNS) tumor. One of the most effective and widely used treatments for CNS cancer is radiation therapy (XRT). Because the human brain takes decades to fully develop, children who receive brain XRT are particularly at risk for serious, long term, side effects. These survivors are less likely to obtain a driver’s license, marry, hold down a job, or live independently as adults and significantly more likely to require special education services, suffer from depression, thyroid gland, reproductive organ and growth hormone disorders, hearing or vision impairments, secondary cancers and have a higher incidence of stroke compared to their healthy peers. Concurrent to the importance of finding a cure for pediatric brain cancer is the critical importance of understanding how brain cancer treatment affects the developing brain (a subject The Monje Lab is also working on…) so that scientists may develop better ways to protect pediatric patients from experiencing these devastating side effects and treat them more effectively when they do.
10. The Difference is in the People
The doctors, researchers and advocates I met during the Stanford Nanocourse are nothing short of heroic. It is truly breathtaking to be in a room full of parents who have lost the most precious thing in the world to them…their child…then add to the mix doctors and researchers who have dedicated their entire careers to finding a cure for pediatric cancers, and you may then begin to understand how humbled I was to be in their midst. It is hard to put into words how inspired I was by their, across the board, selfless dedication, compassion and commitment to making a difference in the world of pediatric brain cancer. It was my distinct privilege to learn along side these amazing individuals, to hear their heartbreaking yet beautiful journeys with pediatric cancer and the triumphs and frustrations of researching one of life’s most mysterious and deadliest cancers. We laughed, we cried, we learned, we pondered, but mostly we came together for a common cause…to grow the community that is shining a light on pediatric brain cancer to find a cure…And although I’d give anything to have never even heard of DIPG, I left Stanford full of hope and forever changed by what I learned and the partnerships forged during my time there.
My heartfelt thanks to Dr. Monje, the Wetzel family, the McKenna Claire Foundation and all of the presenters and participants of the 2014 Pediatric Cancer Nanocourse for this once in a lifetime opportunity…