The Keller Laboratory at cc-TDI: Jan 6, 2014

Monday, January 6, 2014

International group of pediatric brain cancer researchers receives $300K toward a cure

press release

Parents of children who died from rare cancer believe greater investment in quality research is critical

PORTLAND, Ore. – An international consortium of researchers focused on identifying new molecularly targeted drugs to treat the most fatal form of childhood brain tumor, diffuse intrinsic pontine glioma, or DIPG, has been awarded nearly $300,000 by The Lyla Nsouli Foundation for Children's Brain Cancer Research, based in London, England. The foundation was established in memory of 3-year-old Lyla Nsouli, who died in January 2012 after a devastating five-month battle with DIPG.

Lyla’s parents, Nadim and Simone Nsouli, are hopeful their contribution will help bring researchers closer to a cure: “Facing her sudden, brutal diagnosis without any real option for treatment or survival is not an experience any child or their family should ever have to bear. Significantly greater investment in quality research is vital to improving the prognosis for children like Lyla. We are determined that research can provide treatments and eventually a cure for this cruel childhood cancer.”

To date, no treatment does more than incrementally increase survival of children with DIPG. One day a child may have a headache or unsteadiness, but the next day a family's life and plans are tragically changed. A group of international researchers called the DIPG Preclinical Consortium hopes to change this.

“Our first phase of drug screening and tumor DNA sequencing couldn't have been possible without the support of the Lyla Nsouli Foundation, the Cure Starts Now, Accelerate Brain Cancer Cures and CureSearch Foundations. Now that we have drug leads, the hard work of validating these begins. The Lyla Nsouli Foundation has been with us every step of the way, both in terms of support and accountability — both matter,” said consortium coordinator Charles Keller, M.D., associate professor of pediatrics at Oregon Health & Science University Doernbecher Children’s Hospital and the OHSU Knight Cancer Institute.

“The members of the Children’s Oncology Group CNS committee express a deep sense of gratitude to the Lyla Nsouli Foundation for funding the DIPG Preclinical Consortium,” said Amar Gajjar, M.D., chair of the brain tumor committee for the National Cancer Institute-supported Children's Oncology Group (COG). “The grant from the foundation has sparked a global effort to find new and effective therapies using the latest technologies currently available against diffuse intrinsic pontine glioma. The rapid translation of information from research laboratories to a clinical protocol is an often sought aim for advancing cancer cure rates – the grant from the Lyla Nsouli Foundation has made this dream a reality.”

Gajjar and Maryam Fouladi, M.D., co-chair of the COG brain tumor new agents committee and leader of its Pediatric Brain Tumor Consortium, conceived the DIPG Preclinical Consortium with Keller: “Real-time science in partnership with the community for a shared goal of finding a two-drug combination to put into international clinical trials for DIPG.”

Consortium member Jacques Grill, M.D., Ph.D., Institut Gustave-Roussy, Villejuif, France, innovates by creating living cell cultures not from autopsy-derived tumor samples, but from biopsies from the brainstem. This novel approach was initially controversial but is winning acceptance, Keller noted.

“Grill and his colleague, Dr. Darren Hargrave at Great Ormond Street Hospital, London, keep a clear line of communication so that the consortium's results are reported in real time to the European clinical trial groups to inform on that side of the Atlantic,” said Keller. “The scientific teams are diverse due to the pressing nature of the need to understand and treat DIPG.”

Each member will take a different but complementary role to ensure the results of the robotic drug screen of 17 autopsy- or biopsy-derived DIPG cultures can be validated in mouse models.

"This collaboration has been a wonderful opportunity to work together as a community to move the field closer to an effective therapy for this terrible disease. I am hopeful that, together and with the immense support from Lyla Nsouli Foundation, we will make real strides forward now," said Michelle Monje, M.D., Ph.D., Stanford University Beirne Faculty Scholar in Pediatric Neuro-Oncology, Stanford Cancer Institute, Lucile Packard Children's Hospital.

"The DIPG Preclinical Consortium offers hope where once there was very little. When my son, Andrew, was diagnosed with DIPG in October 2007, I never imagined that such a collaboration would exist a few short years later — a collaboration where exceptional science and a remarkable patient community meet in partnership to change the future for children like Andrew and Lyla," said DIPG parent Sandy Smith.

# # #

Consortium members include: Keller, Kellie Nazemi, M.D., Nathan Selden, M.D., Ph.D., Doernbecher Children’s Hospital, Oregon Health & Science University; Monje, Stanford University; Grill, Institut Gustave-Roussy; Oren Becher, M.D., Duke University Medical Center; Cynthia Hawkins, M.D., Ph.D., University of Toronto; Xiao-Nan Li, M.D., Ph.D., Baylor College of Medicine; Esther Hulleman, VU Cancer Center Amsterdam; Eric H. Raabe, Johns Hopkins University; Katherine Warren, Paul Meltzer and Martha Quezado, NIH; and Marta Alonso, University of Navarra, Madrid, Spain.

The DIPG Preclinical Consortium is funded by the Lyla Nsouli Foundation for Children’s Brain Cancer Research, the Cure Starts Now, Accelerate Brain Cancer Cures and CureSearch Foundation.

ABOUT OHSU DOERNBECHER CHILDREN’S HOSPITAL

OHSU Doernbecher Children's Hospital ranks among the nation’s "Best Children’s Hospitals."* It is one of only 22 National Institutes of Health-designated Child Health Research Centers in the country and ranks 39th for NIH awards to children's hospitals and their university-affiliated department of pediatrics.**

Nationally recognized physicians and nurses at OHSU Doernbecher provide a full range of pediatric care to tens of thousands of children each year from Oregon, Southwest Washington and around the nation in a family-centered environment. OHSU Doernbecher specialists also travel throughout Oregon and Southwest Washington, caring for more than 3,000 children at more than 200 outreach clinics in 15 locations. Neonatal and pediatric critical care experts provide round-the-clock consultations to community hospitals statewide through OHSU Doernbecher's state-of-the-art telemedicine network.

*U.S. News & World Report 2013-14 Best Children’s Hospitals

** National Association of Children’s Hospitals and Related Institutions (NACHRI)

You Can Participate in our Novel Therapeutics Studies !

One would like to think that tangibly better treatments for rhabdomyosarcoma, medulloblastoma and other childhood cancers can be found in a matter of years, instead of tens of years. Finding new treatments starts with research, perhaps even a new research approach to identifying effective new treatments. The Children's Cancer Therapy Development Institute focuses on finding molecules in childhood cancers that can be directly turned off or on by drugs so that the tumor stops growing. Behind our novel approach is the use of genetically-engineered mice. Our Pediatric Preclinical Testing Initiative uses mice modified from before birth so that at a certain age, and in a certain tissue, the same mutations found in a child’s cancer are activated in the mouse. These special mouse models of childhood cancer can be used to test a treatment to see whether the tumor growth and spread (metastasis) can be reversed. The specific aspect of these mice having normal immune systems is a real plus, too, because white blood cells play an important role in how tumors evolve and respond to therapy.

Our program is designed around community participation. Through the Children's Cancer Therapy Development Institute, you can contribute directly to this grass-roots initiative. Donations through small gifts or grants will assist in studying compounds that may be effective in treating such childhood cancers as alveolar rhabdomyosarcoma, embryonal rhabdomyosarcoma, or medulloblastoma (the alveolar rhabdomyosarcoma model was featured by Dr. Keller's long time collaborator and former mentor, 2007 Nobel laureate Mario Capecchi, in his Nobel Prize lecture {see 16 minutes onward}.)

For additional information regarding supporting this program please contact Charles Keller at charles@cc-tdi.org. Results obtained through these studies will be shared with the National Cancer Institute’s Cancer Therapy Evaluation Program, as well as the Children’s Oncology Group, which designs clinical trials for childhood cancer.