DIPG News

ALSF Announces 2011 ‘A’ Awards To Researchers In San Francisco Area

Researchers at Stanford University and the University of California at San Francisco receive prestigious awards to examine childhood cancers

Wynnewood, PA (December 2011) – Alex’s Lemonade Stand Foundation for Childhood Cancer (ALSF) today announced the recipients of the ‘A’ Award, a groundbreaking pediatric cancer research grant designed to jumpstart the careers of promising scientists in the pediatric cancer field. Michelle Monje, MD, PhD of Stanford University and William Gustafson, MD, PhD of the University of California at San Francisco were chosen from nearly 30 applicants as the 2011 recipients of the grant which totals $375,000 over the course of three years. Dr. Monje’s research will target Diffuse Intrinsic Pontine Glioma (DIPG) while Dr. Gustafson will examine neuroblastoma.

The ‘A’ Award joined a prestigious line of medical and nursing grants from Alex’s Lemonade Stand Foundation in 2009. The award was created in an effort to find the best and brightest young researchers and encourage them to build life-long careers in the pediatric cancer field. The Foundation believes that young researchers are integral components of finding new treatments and cures, and by providing support for their research these investigators will utilize their talents toward pediatric oncology.

Dr. Monje, an Assistant Professor of Neurology and Neuro-Oncology at Stanford University, will focus her research on DIPG, a highly aggressive and difficult to treat brain tumor. DIPG is the second most common malignant brain tumor in children and the leading cause of pediatric cancer death with a survival time after diagnosis of less than a year. Monje and her team have developed the first published experimental model system to study DIPG and have thus discovered molecular factors that drive tumor growth. Now, they will use this experimental model system to test therapeutic strategies combining two drugs to target both the cells responsible for tumor initiation and those responsible for tumor expansion. If successful, Monje would seek to translate her findings into a clinical trial for children battling DIPG.

Dr. Gustafson will examine high-risk MYCN amplified neuroblastoma, a deadly form of childhood cancer which frequently becomes resistant to chemotherapy and radiation. In his research, Dr. Gustafson will develop models of this high-risk disease for pre-clinical testing, and he will utilize cutting-edge chemistry to direct targeted therapy against the Aurora A protein, known to be critically important both in driving cell growth and in maintaining high MYCN levels. Through these studies, Dr. Gustafson will ultimately work toward novel and clinically tolerable therapies which target drug-resistant neuroblastoma.

Along with the funds provided to ‘A’ Award recipients, the award will also include access to ALSF’s Scientific Advisory Board for periodic consultation and a choice of reference books to enhance the researcher’s personal pediatric oncology library. New in 2011, the Foundation will also give recipients the choice of equipment to aid in their research (up to $10,000 value), funding to attend one medical conference of their choice and the opportunity to meet other ‘A’ Award recipients to collaborate and share ideas.

The ‘A’ Award will mark the final grants allocated from Alex’s Lemonade Stand Foundation for 2011. However, the Foundation will begin accepting applications for its newly announced Bridge Grant program for NIH childhood cancer research applications that received excellent scores but did not receive funding on December 15, 2011. In an effort to keep the projects of these researchers on track while they reapply for funding, ALSF’s Bridge Grant will provide $100,000 over a 12 month period. Applications will be taken on a rolling review basis with a deadline of January 9, 2012 or until capacity is reached. A total of three grants will be funded in this cycle, with a second cycle planned for the summer of 2012.

For more information on the ‘A’ Award, Bridge Grants or Alex’s Lemonade Stand Foundation’s grant program, visit: www.ALSFGrants.org.

Alex’s Lemonade Stand Foundation 2011 ‘A’ Award Recipients

Michelle Monje, MD, PhD, Stanford University, Palo Alto, CA

A Combinatorial Approach to Target the Tumor-Initiating and Transit Amplifying Cellular Subpopulations in Diffuse Intrinsic Pontine Glioma (DIPG)

Diffuse Intrinsic Pontine Glioma (DIPG) is the second most common malignant brain tumor in children and the leading cause of pediatric cancer death. We have developed the first published experimental model system to study DIPG, and using this have discovered some of the molecular factors that drive DIPG tumor growth. We now propose to use our mouse model system to test a therapeutic strategy combining two drugs. The purpose of this proposal is to develop a strategy that will target two types of cells in the tumor – those responsible for tumor initiation, and a distinct population responsible for tumor expansion. If efficacious, we would seek to translate the findings quickly to a clinical trial for children suffering from DIPG.

William Gustafson, MD, PhD, University of California San Francisco, San Francisco, CA

Blockade of p53 and Aurora A in Therapy Resistant Neuroblastoma

High-risk MYCN-amplified neuroblastoma is typically responsive to therapy at diagnosis, becoming resistant to chemotherapy/radiation at relapse. Mirroring human disease, the well established TH-MYCN model of neuroblastoma, developed in our lab, is responsive to conventional chemotherapy. To cure MYCN-amplified high-risk neuroblastoma, we propose to: 1) Develop models which accurately reflect the genetics and behavior of relapsed, chemotherapy refractory disease. I have developed a drug-resistant version of the TH-MYCN model by crossing it with models defective in p53, leading to a defective response to chemotherapy, and mirroring a similar defect in resistant childhood disease. I plan to characterize the response of this model to conventional chemotherapy as well as novel, targeted therapies including those subsequently described. 2) Development of novel and clinically tolerable therapies which target drug-resistant neuroblastoma. I propose to use cutting-edge chemistry to direct targeted therapy against the Aurora A protein, known to be critically important both in driving cell growth, and in maintaining high MYCN levels. I have already generated a new class of Aurora A inhibitors which block both Aurora functions (current drugs only block cell growth) which we predict will have improved activity against MYCN amplified neuroblastoma.

DIFFUSE INTRINSIC PONTINE GLIOMA:
COLLABORATION IS LEADING TO CHANGE

Dr Loice Swisher whose daughter Tori is a ten year medulloblastoma survivor. Loice is an FDA Patient Representative and emergency medicine physician. She is pictured here on a family vacation in Utah.

“It’s been almost two years since Sam was diagnosed in December 2006. The only improvement that I’ve seen during this time is that we have this wonderful site!” [the DIPG Internet Yahoo support list and discussion group]

So said “Sheila” (in December 2008), whose young grandson had died in February 2008 from a diffuse intrinsic pontine glioma.

A diffuse intrinsic pontine glioma, known as DIPG, is perhaps the most feared pediatric brain tumor because of the dismal survival statistics and devastating clinical course. This tumor tends to strike four to ten year olds with approximately half of these young children dying in the first year and 80-90% by the end of the second.

Despite more than 200 trials, no treatment has been found to be effective for long term survival in DIPG. For some children, steroids and radiation allow for a ‘honeymoon’ with relief of symptoms. But this is often followed by a relentless advancing of the disease and tragically, death months later.

Basic science research into this tumor has been frustratingly difficult. A significant hurdle has been the lack of tumor tissue on which to carry out tests.

In 1993, the standard of care for DIPG in the United States changed, as biopsy provided no improvement in survival over neuro-imaging in typical pediatric diffuse pontine tumors. Since that time, biopsies of pediatric DIPG have been uncommon resulting in the scarcity of tumor material for research. At the time “Sheila” wrote, there were no published reports on cell lines, no animal models and no molecular/genetic studies.

The changes in the medical community’s approach to a disease are often evident much before the patient community is aware of them because the time from concept to study to publication of a research paper can take years. In 2008, change was beginning in DIPG research. The heart-wrenching post from grandmother “Sheila” launched an effort towards earlier awareness of research endeavors as well as international advocacy collaboration.

In 2005 the biopsy debate had heated up again. St Jude Children’s Research Hospital in Memphis, Tennessee (USA) responded with a concerted effort to approach families for post-mortem tumor donation for research resulting in more molecular information on DIPG. Since many children die at home, far from St Jude, the emotional and logistical challenges were numerous.

A family responded to the financial issues raised by these challenges by establishing a foundation called Tyler’s Treehouse (established in 2006), specifically started to fund the logistical aspects of this study.

Over the ensuing years, many families with DIPG children have provided the ultimate gift to the research community involved with these studies of their child’s tumour tissue. Some families as far away as Australia and South America have donated their child’s tissue. The St. Jude efforts haven’t lead to publication yet, however, The Hospital for Sick Children (“Sick Kids”) in Toronto, Canada published the first whole genomic analysis of DIPG tumors in February 2010.

Their French colleagues took a different approach, with a clinical trial including upfront stereotactic biopsy of pediatric DIPG. In the July 2007 issue of the Journal of Neurosurgery the surgical results were published. With 33 children there was no mortality and only two children had transient morbidity.

The combined effect of the French stereotactic biopsy results and the molecular analysis studies from “Sick Kids” in Toronto has lead to renewed efforts for future clinical trials to include molecular analysis from stereotactic biopsy samples.

The development of animal models is also emerging.

At the 2008 ISPNO (International Symposium on Pediatric Neuro-Oncology) conference in Chicago (USA), Dr. Oren Becher won the best basic science presentation award for his genetically engineered mouse model of brainstem glioma. The excitement of potentially being able to study this tumor in a mouse model has resulted in requests for Dr Becher’s mice from several others interested in studying brainstem glioma.

For some time, the non-availability of resected tumor tissue for the development of cell lines has met with failure, even to the point of new researchers being discouraged from pursing this direction.

In the summer of 2009, Stanford University in California revealed that Dr. Michelle Monje had been able to culture neurospheres from post-mortem pediatric DIPG tissue using a stem cell technique. This breakthrough in DIPG research at Stanford has lead to an EGFRviii vaccine being introduced to the pediatric brain tumor community for the first time as well as other research. Some of this has been funded through the Kyle O’Connell Foundation.

Truly exciting events have been two international meetings of researchers and clinicians to discuss DIPG. The Fondo Alicia Pueyo hosted the first conference in Barcelona, Spain in February 2009. The second event was hosted by The Hospital for Sick Children in Toronto with funding support by Just One More Day and B.R.A.I.N.child.

We are now seeing a change in DIPG research – and the international collaboration of parents, advocates, clinicians and researchers that is making this happen.

 

Written by: Dr. Loice Swisher

Jordan Malave Earns His Wings After Long Battle With DIPG

With great sadness, the Cristian Rivera Foundation announced that Heaven gained another DIPG Angel on Thursday November 17. Jordan Malave passed away at 6:30 on Thursday morning, bringing to an end his three-year battle with DIPG. He fought for an exceptionally long time and showed incredible bravery and strength in the face of this terrible disease. Cristian Rivera Foundation founder John “Gungie” Rivera had become close to Jordan and his parents, Leeana Castro and Jayson Malave, and even saw Jordan after his kindergarten graduation this past June. Jordan reminded John very much of Cristian, and watching him suffer was like living through Cristian’s illness all over again. John and the entire Cristian Rivera Foundation extend their sincerest condolences to Jordan’s family as they are once again reminded how horrible DIPG is and why it needs to be cured within our lifetime.

Support the National Childhood Brain Tumor Prevention Act

Dear Pediatric Cancer family or family friend,

WE NEED YOUR HELP. The National Childhood Brain Tumor Prevention Act is currently working its way through Congress. If passed, this Act would allocate $25 million a year for five years for the FIRST comprehensive research into the causes of brain tumors in children, including genetics, nutrition, the environment, and more. It will give us answers about better treatments and even prevention. To get this legislation passed we need your help. If families affected by childhood brain tumors—and all those who know them, love them, and understand what they go through–could write a letter, an e-mail, or make a phone call to their federal representatives, the future of our country’s children would be brighter. As stated by world renowned neurosurgeon Dr. Patrick Kelly, “once [a child] is diagnosed with brain cancer, it’s too late.”

  • Thousands of kids are diagnosed with a brain tumor each year and more than 40% of them die.
  • The average age of a child that dies from a brain tumor is 4.
  • More than 60% of those that survive face life-long complications and side effects.

That’s why we’re asking you to contact your Congressperson and Senators to let them know that you want to see this Act made into law. For more information and quick outlines to write a letter or e-mail, or make a call, visit www.mirasmovement.org/CBTPNA.html. For further assistance or if you have questions, e-mail cbtpna@mirasmovement.org or call (607) 319-4804. Thank you for helping us change the future for children with brain tumors!

September is Childhood Cancer Awareness Month

September is Childhood Cancer Awareness Month, a time to reflect on all the young lives that have been taken by all different kinds of cancer, including Pontine Glioma. In the same way that breast cancer is associated with pink and AIDS is associated with red, the color that signifies Childhood Cancer Awareness Month is gold. So be sure to wear a gold ribbon to show your support for children and families dealing with cancer, as well as those whose loved ones have been lost. You can also take the opportunity to support Pontine Glioma research through the Cristian Rivera Foundation by clicking the “Shop” tab and purchasing a wristband or t-shirt.