Children’s Brain Tumor Project Lab Update: Fall 2016

Posted in Research

As many of you probably read about on Facebook, on September 8 we treated the final patient in our Phase I clinical trial of convection-enhanced delivery (CED) for diffuse intrinsic pontine glioma (DIPG). The trial, which had enrolled 27 patients over the past four years, was designed to test the safety of CED as a means of delivering a cancer-fighting drug directly to the site of a DIPG tumor. Four patients received a second infusion, bringing the total number of treatments to 31. This trial has generated a wealth of information, and we have already started publishing academic papers about it, sharing our discoveries with other researchers in the spirit of collaboration that drives this project. Details of the infusion technique, the imaging studies, and other learning that will assist other researchers worldwide have already appeared in academic journals. The “big one,” providing data on the safety of the procedure, will probably take a year or more to prepare for publication. But with no dose-limiting toxicity in any patient, we feel confident that the technique is a safe way to deliver cancer-fighting drugs to a DIPG tumor. The next steps are to identify the most promising drugs to test in future phases of this trial. Fortunately, thanks to our generous donors the legwork on that has already begun. Be sure to read our update on the results of our “summer sprint,” the unprecedented effort that brought a dedicated team of young researchers into the lab in July and August to help us lay the foundation for future trials. These talented young investigators didn’t work only on DIPG, however. The drugs they evaluated, the molecular modifications they tested, and the other innovative lines of research they pursued will be of invaluable help as we continue to forge this path. Thank you all, again, for the continued loyal support that allows us to do this important...

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New Publications From the CBTP, Fall 2016

Posted in Research

“Exploring the role of inflammation in the malignant transformation of low-grade gliomas.” Journal of Neuroimmunology, 2016 Aug 15;297:132-40. Epub 2016 May 25. “A novel magnetic resonance imaging segmentation technique for determining diffuse intrinsic pontine glioma tumor volume.” Journal of Neurosurgery, Pediatrics, 2016 Jul 8:1-8. [Epub ahead of print] “A Novel Methodology for Applying Multivoxel MR Spectroscopy to Evaluate Convection-Enhanced Drug Delivery in Diffuse Intrinsic Pontine Gliomas.” AJNR American Journal of Neuroradiology, 2016 Jul;37(7):1367-73. Epub 2016 Mar 3. “Gliomatosis cerebri: A consensus summary report from the First International Gliomatosis cerebri Group Meeting, March 26-27, 2015, Paris, France.” Pediatric Blood Cancer, 2016 Jul 28. [Epub ahead of print] “Convection-Enhanced Delivery for Diffuse Intrinsic Pontine Glioma Treatment.” Current Neuropharmacology, 2016 Jun 13. [Epub ahead of print] “Clinical Genomics: Challenges and Opportunities.” Critical Reviews in Eukaryotic Gene Expression, 2016;26(2):97-113. Click on any of the links above to read summaries of these papers on...

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Exciting Results from the ”Summer Sprint”

Posted in Research

Thanks to a number of grants and private donations, in July and August the CBTP lab team was joined by several young researchers working on specific projects to advance the field of pediatric neuro-oncology. This “summer sprint” was an unprecedented effort that produced some excellent results. Umberto Tosi, funded by a POST grant from the Alex’s Lemonade Stand Foundation, worked on a project to improve the measurement of drug delivery to the brain via “theranostic” (therapeutic and diagnostic) agents. The usual method of determining whether a drug has been successfully delivered is to wait for a clinical response, a “wait-and-see” approach that is neither timely nor precise. If researchers could modify a drug to make it fluorescent—and therefore visible on PET or MRI imaging—they would be able to see in real time whether that drug has reached its target. The key is to make delivery of the drug visible and measurable without reducing its effectiveness. Working with collaborators at Weill Cornell Medicine’s Molecular Imaging Innovations Institute (MI3), Umberto tested several modified versions of the drug dasatinib both in vitro (in petri dishes) and in vivo (in animal models). Several of them acquired their new imaging potential while retaining their therapeutic properties, and they will advance to further rounds of testing on several different malignancies. The modification technique was then performed on panobinostat, a drug that has already shown significant promise in the treatment of DIPG. As we had hoped, the modified panobinostat was successfully imaged with PET/CT and its therapeutic properties were not altered. We hope this new compound will allow for a more precise treatment of DIPG. Raymond Chang tested ways to combine drugs to defeat DIPG, which has defense mechanisms that allow it to evade otherwise effective drugs. Research has identified certain molecular signaling pathways that could be promising targets for drug therapy, but the tumor has alternative pathways that allow it to grow despite use of a single drug. Raymond tested several drugs, individually and in combination, on DIPG cell lines grown in our lab and discovered one potent inhibitor of DIPG growth in vitro. After combining that drug with several other classes of drugs, he found a MEK-inhibitor that showed substantial synergistic effects. Raymond will continue his work in the lab, where he is now using xenograft mouse models of DIPG to demonstrate that this drug combination will be more effective in reducing tumors than either drug individually. Raymond’s summer assignment was funded by the American Brain Tumor Association. Emilie George established in vitro cell models of gliomatosis cerebri (GC). Together with the Greenfield lab team, Emilie initiated a drug screening protocol to begin testing chemotherapeutic agents on this newly developed cell model. This project...

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Family Update: Fall 2016

Posted in From the CBTP Families

They say that life is a highway and its milestones are the years, And now and then there’s a toll-gate where you buy your way with tears. —Joyce Kilmer (“Roofs,” 1917) September is all about milestones, with its back-to-school firsts and the excitement of new beginnings. This year we have a special milestone: After 40+ years in my childhood home, including 14 years raising our family in it, the Andersons have moved! That house was a home base we had only ever planned on expanding, but Hurricane Irene five years ago, then Sandy a year later, was the beginning of the end. We began to mourn our home then, but we never could have imagined what was yet to come. I’ve learned a lot in the past five years about “the best laid plans.” On July 1, 2008, Lily LaRue Anderson (“twin B”) was born—naturally and epically, butt first and fists flailing—seven minutes after Brady Cooper. I had greeted each of my three prior babies with a proper “Happy Birth Day!” but I asked this one, “who ARE you”? I did not know it then, but this was to be the ride of my life. Still, it wouldn’t be fair to say that this is the date that defines me, since no one ever prepares you for the dates you never knew existed. The date of diagnosis. The date of radiation, chemo, mask fittings… All the dates of every single MRI. The day something changed. The day she couldn’t walk. The last day she said my name. The day she died: April 6, 2015. All these days make me. Lily LaRue was diagnosed on May 4, 2014. We were in Hershey, Pennsylvania, celebrating Kentucky Derby weekend (as we always did) and she fell at the pool. We wanted to make sure she could go on roller coasters the next day, so we took her to the hospital. (We hoped no one would think we were silly, overly cautious parents, and the irony of that is NOT lost on me.) It was there that we were introduced to “the room.” The room may be different for everyone in its geography, smell, or shape, but we all know that room. It’s where they took us to tell us they’d found a lemon-sized mass in Lily’s brainstem. No, there were no symptoms. No, she was FINE. No, do it again, you’re wrong… We traveled thousands of miles in her remaining 337 days seeking a cure, and we would have traveled a million more. We researched and reached out from a place of acute and overwhelming confusion and knowledge, in a place and time we never knew existed. Pediatric cancer. Brain tumor. Cannot...

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Elizabeth’s 25th Birthday

Posted in About EH, From the Minter Family, Updates

Dearest Elizabeth, Can it be that today you would be 25? So hard to believe. It’s even harder to accept that this is the fourth birthday without you. We still think of and miss you everyday. Our greatest fear is that our memories will fade and that others will forget. In the last few weeks our fears of others forgetting have been muted by so many acts of kindness and remembrance. Thank you all. Elizabeth, clearly your capacity for friendship and courage in facing the worst had an Impact. We take comfort in the knowledge that your short life was well lived. We still wait for signs from you. In recent days we have seen several “sun dogs” on the ski slopes. We call them “sun Angels”. Each time we see one, we think it’s a kind of wink, smile, or kiss from you. We never ask ourselves “why” you were the unlucky one who got this awful, deadly brain cancer. However, we do dare to wonder, “What if there had been better treatment options or a cure?” IMAGINE……. We know a cure was your dream up until the very end. Please be assured that we and so many others share and are committed to that vision. Love, Mom and Dad P.S. We know that many are disappointed that we are not hosting the EH Party this Spring. Stay tuned, as we are a planning a party in the autumn to celebrate the 5th anniversary of Elizabeth’s Hope. No Elizabeth–we could never forget you. Memories and your spirit bless us...

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A special message to the Elizabeth’s Hope community

Posted in Updates

Dear Friends, It’s hard to believe it was five years ago this month that Elizabeth Minter was diagnosed with gliomatosis cerebri — an earth-shattering diagnosis for her, her family, and all the many people who loved her. That diagnosis started a 17-month journey, which this remarkable young woman traveled with grace, optimism, and hope — always hope. Five years later, it’s her hope that lives on. Elizabeth’s legacy is Elizabeth’s Hope, but it’s also the Children’s Brain Tumor Project, which grew out of what she and her family started. More than 3,400 people have made donations to the Children’s Brain Tumor Project — and many of them found us through Elizabeth’s Hope. Many more (too many) found us when their own family, or someone in their community, heard the same terrible news that the Minters received in December 2010. The generosity of these thousands of people have sustained our work and allowed for significant growth and accomplishment in the lab. We are so deeply grateful for your confidence, and your support. I know five years can feel like a lifetime when measured in the absence of a child, but in scientific terms it’s the blink of an eye. Laboratory research proceeds at a deliberate pace and typically takes decades to unfold. This project is very different. In these last five years we have made an unimaginable amount of progress and now have a thriving lab pursuing multiple lines of inquiry across a broad range of pediatric tumors. We are seeing in the lab what we suspected from the beginning: that each cancer is different, that we must focus on getting as much information as we can about every individual tumor, and that we will someday be able to tailor the right treatment to a specific patient. We are tremendously fortunate to have the new Weill Cornell Precision Medicine Institute as our partners in this effort. In 2012 Elizabeth’s tumor was the first GC sample ever sequenced, and we’ve learned a tremendous amount from it. Thanks to the Precision Medicine Institute, and the family power of Elizabeth’s Hope and the Children’s Brain Tumor Project, we are now able to sequence EVERY pediatric brain tumor treated at Weill Cornell. This gives us access to an unprecedented amount of information, and we are working hard every day to interpret it, understand it, and match new treatment options to different mutations. We are now growing GC and DIPG tumor cells in the lab. Having these cell lines available is ground-breaking — we can watch mutations as they happen, test drugs and drug combinations against them, and understand more every day about how these cancers progress. When I look through the microscope at these...

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