Patient Groups and Researchers Join Forces to Speed Treatments for Rare Pediatric Brain Tumor

(reposted from here) 

Four Organizations Fund International Research Consortium to Improve Lives of Children Suffering From Diffuse Intrinsic Pontine Glioma (DIPG) 

  

January 23, 2012 (Washington, DC, and Bethesda, MD) – Accelerate Brain Cancer Cure (ABC2), CureSearch for Children’s Cancer, The Cure Starts Now Foundation and The Lyla Nsouli Foundation for Children’s Brain Cancer Research today announced their collaborative funding to support groundbreaking research aimed at dramatically improving the lives of children suffering from Diffuse Intrinsic Pontine Glioma (DIPG) – one of the most devastating pediatric cancers.  Together, the four organizations have committed $229,000 to support the work of the DIPG Preclinical Consortium, the only international scientific group focused on preclinical development of targeted therapy combinations for DIPG.  The goal of the research is to test and then move the most effective therapy forward to early phase clinical trials in the next 18 – 24 months.

Children with DIPG have a uniformly dismal prognosis with a median survival of 9 months.  A DIPG tumor grows amidst the nerves in the pons (middle) of the brain stem, and therefore cannot be surgically removed. Radiotherapy provides only temporary improvement of symptoms.  No chemotherapy has ever proven effective. Novel therapies are desperately needed. “The scientific community has truly rallied around this cause.  The mandate for a novel therapeutic approach was born in the Children’s Oncology Group brain tumor committee under the bold leadership of Dr. Amar Gajjar.  With the consortium co-leadership of clinical trialist Maryam Fouladi and the accountability to DIPG patients and their family, this program is moving unexpectedly quickly towards its goal,” says Charles Keller, MD, Associate Professor and leader of the Pediatric Cancer Biology Program, Pape' Family Pediatric Research Institute in the Department of Pediatrics at Oregon Health & Science University.

“If we succeed, it will be because families that have donated their children’s tumor gave us this opportunity.  We are reminded every day that the cultures we study are parent-directed Legacy Gifts of the most selfless kind from children who current therapy could not save (the brain stem being vital to life; therefore, tumor donation can only occur at autopsy).  What  ABC2 , CureSearch for Children’s Cancer, the Lyla Nsouli Foundation, and The Cure Starts Now have done to make our consortium possible, and so quickly, is unprecedented – and greatly appreciated,” adds Dr. Keller.

The research project entitled, "Rapid Preclinical Development of a Targeted Therapy Combination for DIPG" was launched with initial support from The Cure Starts Now Foundation. Two additional European labs were added to the project with funding from The Lyla Nsouli Foundation for Children’s Brain Cancer Research (based in London, UK).

The funding from ABC2 and CureSearch for Children’s Cancer added a cutting-edge functional genomics component that will prioritize potential new drug targets. “We are proud to support this multi-national team of researchers in their efforts to rapidly develop effective drugs to treat children suffering from DIPG,” said Max Wallace, CEO of ABC2. “By combining forces with our non-profit partners, ABC2 looks forward to leveraging the resources and expertise of all the organizations to improve the lives of children with cancer.”   John Lehr, president and CEO of CureSearch for Children’s Cancer echoed Wallace’s comments saying that “developing new drug targets is an integral step to providing children with DIPG a  better prognosis.  CureSearch is committed to funding research in rare cancer types so that one day, all children will be guaranteed a cure.”

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About the DIPG Preclinical Consortium

The multi-national consortium is identifying potentially important biological pathways in DIPGs that are readily targetable with currently available molecularly-targeted agents. In addition, the consortium has successfully grown human DIPG tumors from autopsy materials in the petri dish and has developed mouse models of DIPG – a key resource to functionally testing potential therapies.

Since the number of children with this unfortunate disease is limited, and the number of available targeted agents is quite large, the consortium hypothesizes that it can identify a promising combination of molecularly-targeted agents using functional genomics to prioritize targets. The ultimate goal is to move the most effective single agent or combination therapy forward to early phase clinical trials in the next 18-24 months.

The DIPG Preclinical Consortium team includes:

Charles Keller MD, Kellie Nazemi MD and Nate Selden MD, PhD at Oregon Health & Science University

Oren Becher MD, Duke University Medical Center

Michelle Monje MD, PhD, Stanford University

Maryam Fouladi MD, Cincinnati Children’s Hospital Medical Center

Cynthia Hawkins, MD, PhD, University of Toronto

Xiao-Nan Li MD, PhD, Baylor College of Medicine

Dannis G. van Vuurden MD, MSc, & Esther Hulleman, VU Cancer Center Amsterdam

Jacques Grill, Institut Gustave-Roussy, Villejuif, France

For More Information about the Research Funding Partners:

Accelerate Brain Cancer Cure: www.abc2.org

CureSearch for Children’s Cancer: www.curesearch.org

The Cure Starts Now Foundation: www.curestartsnow.org

The Lyla Nsouli Foundation for Children’s Brain Cancer Research: www.lylansoulifoundation.org

Dr. Keller leads team that focuses on the incurable 20 percent in pediatric cancer

[ re-posted from the story in OHSU School of Medicine News by Jennifer Smith ]


08/29/11 Portland, Ore.

Charles Keller, MD, FAAP, knows what he wants. Or rather, he knows what the children and families of those with rare, incurable pediatric cancers want – effective, personalized treatment. The cure rate for childhood cancers as a group is approaching 80 percent. The Pediatric Cancer Biology (PCB) Program in the Papé Family Pediatric Research Institute at OHSU addresses the causes of mortality in the remaining 20 percent of children. Their work is getting noticed – just a year after joining OHSU, research by Dr. Keller and the PCB team have published 16 papers in high-impact scientific journals.


“We’re looking for the quantum leap for the diseases that can’t be cured,” said Dr. Keller, Associate Professor, Department of Pediatrics and Sada and Rebecca Tarshis Professor in Pediatric Hematology Oncology.


Hepatoblastoma is one of four diseases of priority for the PCB Program, which Dr. Keller leads; the others include sarcomas, brain stem gliomas and neuroblastoma.


“With the leading researchers we already have and the right recruiting focus, we can create the first-ever U.S. lab to study liver stem cell biology in a focused, results-driven way,” said Dr. Keller.


A number of factors led to Dr. Keller’s vision for a program with a focus on Hepatoblastoma when he joined OHSU in August 2010. He recognized the rich environment for liver stem cell research at OHSU in the Oregon Stem Cell Center, led by Center Director Markus Grompe, MD, Professor, Department of Pediatrics.


Dr. Keller also recognized the paucity of U.S. labs dedicated to such focused research. Perhaps the best known work on Hepatoblastoma, he said, is found in the lab of Dr. Marie Annick Buendia at the Pasteur Institute in Paris; other notable research is being done in Germany, Thailand, Japan and Australia.


OHSU’s growing focus on molecular-targeted therapy, in particular at the OHSU Knight Cancer Instiute, also attracted Dr. Keller. Conventional treatments – chemotherapy, surgery and radiation – are not generally effective for the most devastating childhood cancers.


The research necessary for personalized therapy requires coordinated efforts on several fronts. The Pediatric Preclinical Testing Initiative (PPTI), a part of the PCB Program, investigates new drugs for treating childhood cancers. The PCB Program launched the Knight-affiliated Childhood Cancer Registry for Familial and Sporadic Tumors (CCuRe-FAST), a tumor bank and registry, in May which will inform the creation of pediatric personalized cancer therapy. CCuRe-FAST is open to all pediatric cancer patients at Doernbecher and OHSU, and has successfully established 34 primary cell cultures as of mid-August.


Dr. Keller is wasting no time in assembling a team of researchers whose expertise can contribute to a productive understanding of rare childhood cancers in order to create a plan to tackle the diseases. His team comes from all types of backgrounds – he enlists biochemists, biomedical engineers, molecular biologists and electrical engineers – and focuses as much on creativity as on science. For example, they are the first National Cancer Institute affiliate to use genetically-engineered mouse models to study tumor growth and to explore treatment options.


And he’s not stopping yet. “It’s my goal to recruit two additional high caliber investigators in the next five years,” said Dr. Keller. “Two additional labs – one focusing on glioma and one on neuroblastoma biology – would move us significantly closer to finding innovative treatments for pediatric cancers.”


In February, Cancer Cell published a landmark study, in which Dr. Keller and the PCB team discovered the cell of origin for childhood muscle cancer. In March, PCB researchers, led by Jinu Abraham, PhD, identified a promising new approach to overcoming drug resistance in children with an extremely aggressive childhood muscle cancer known as alveolar rhabdomyosarcoma. This study was first published online and graced the April cover of Molecular Cancer Therapeutics. And as an unexpected result, their laboratory published in June in the Journal of Biological Chemistry that an antibiotic that inactivates a gene responsible for preventing eye cancer in children can actually improve muscle stem cell generation, with implications for muscular dystrophy, but not apparently putting those patients at risk for rhabdomyosarcoma.


Part of the PCB team’s research takes multi-disciplinary science to a new level – a new species, to be exact. The characteristics of osteosarcoma in canines are remarkably similar to the disease’s pattern in humans, although it is naturally occurring and 10 times more frequent in the four-legged species. Teaming up with Oregon State University veterinarian Bernard Seguin, Dr. Keller and colleagues study drug response in dogs and hope to find treatments that translate to human patients.


As a member of the OHSU Knight Cancer Institute, Dr. Keller works closely with other Knight researchers and supports Knight programs, such as the Knight Seminar Series, which brings experts from across the country to OHSU, with a focus on translational research.


Dr. Keller’s lab, the PCB Program and the PPTI have active blogs, which you can find on the Charles Keller Lab website. The passion and vision Dr. Keller has for his work is evident in person and online. One of his first posts after joining OHSU ended with these words: “Where there is a will, there is a way. Change can be tangible. And we are accountable.”


Pictured above: (top) Dr. Keller and the PCB team, (bottom) Dr. Abraham, Dr. Keller and Elaine Huang, MS, in the lab

PCB Leader joins Northwest Sarcoma Foundation Board

It is with great appreciation that Pediatric Cancer Biology Program Leader, Dr. Charles Keller, has joined in service to the Board of Director of the Northwest Sarcoma Foundation (NWSF). The NWSF and the PCB Program are strategic partners in an NCI-funded outreach effort funded by the Carolyn Price Walker Act.  Working increasingly in synergy with our clinical care partners in Seattle, we hope to make the most advanced treatments and the best patient support available throughout the Pacific Northwest.     

  

OHSU Doernbecher Children’s Hospital Development Therapeutics Program

The principal aim of the Doernbecher Children’s Hospital Development Therapeutics program is to evaluate novel agents for the treatment of pediatric cancer through early phase clinical trials. We conduct Phase I and Phase II trials of potentially promising new drugs for the treatment of all types of childhood cancer.  Doernbecher is one of 21 select institutions throughout North America who comprise the NCI-funded Children’s Oncology Group Phase I Consortium.  Through our participation in COG early phase trials, industry-sponsored trials, and investigator-initiated studies, we hope to find better therapies for the treatment of childhood cancer.

  

The principal investigator of the Doernbecher Children’s Hospital Development Therapeutics program is pediatric hematologist-oncologist, Dr. Suman Malempati.  For a recent discussion by Dr. Malempati on a targeted therapy for childhood sarcomas, see the November 16th  NCI Cancer Bulletin.  Integral, too, to the Development Therapeutics program is Rae Acosta, RN.  

The Keller Laboratory

The Keller Laboratory  at OHSU  studies the driving mechanisms and therapeutic targets in the childhood muscle cancers, alveolar rhabdomyosarcoma and embryonal rhabdomyosarcoma, and the childhood brain tumor, medulloblastoma.