In the traditional funding model, researchers cannot be nimble. If their research leads them to a new and important finding, they cannot redirect funds from other grants to pursue this promising information.
This is where Unravel comes in. Our goal at Unravel is to eliminate obstacles, bottlenecks, and barriers by providing unrestricted funding to help researchers translate ideas into new therapies. We do not ask researchers to take hours to write a grant. We select the best researchers knowing they are working tirelessly to find new, less toxic therapies for the children they are treating and their families.
We have created a Scientific Review Committee compiled of current pediatric research scientists, members of a pediatric research consortium, pharmaceutical industry scientists, and/or clinical trials coordinators. These individuals are in place to help us to identify pediatric cancer scientists with promising work that we can fund.
As a physician-scientist, Dr. Olson cares for children with brain tumors and conducts research that focuses on discovering and developing new cancer therapies. His lab’s work has led to more than a dozen national clinical trials, of which he leads a Phase III trial through the Children’s Oncology Group. Dr. Olson is the founder of Presage Biosciences and Blaze Bioscience.
His lab invented the chlorotoxin-based Tumor Paint, which led to the development by Blaze of the clinical candidate Tozuleristide (BLZ-100), now in human trials. He authored “Clinical Pharmacology Made Ridiculously Simple,” which has been the most used pharmacology board review book for more than 25 years.
Dr. Olson earned his Ph.D. in Pharmacology in 1989 and his M.D. in 1991, both from the University of Michigan. He then completed his residency in pediatrics in 1994 and his fellowship in pediatric oncology in 1997, both at the University of Washington. Dr. Olson is currently a Full Member at the Fred Hutchinson Cancer Research Center, a Professor at the University of Washington, and an Attending Physician at Seattle Children’s Hospital.
The Monje Lab studies the molecular and cellular mechanisms of postnatal neurodevelopment. This includes microenvironmental influences on neural precursor cell fate choice in normal neurodevelopment and in disease states. Areas of emphasis include neuronal instruction of gliogenesis, cellular contributions to the neurogenic and gliogenic signaling microenvironment, molecular determinants of neural precursor cell fate, and the role of neural precursor cells in oncogenesis and repair mechanisms.
As a practicing neurologist and Neuro-oncologist, Dr Monje is particularly interested in the roles for neural precursor cell function and dysfunction in the origins of pediatric brain tumors and the consequences of cancer treatment. As a paradigm of pediatric gliogenesis, we have been focusing on brainstem tumors, whose spatial and temporal specificity bespeak an underlying developmental cause.
I would like to extend my deepest gratitude to Unravel Pediatric Cancer for the continued support of my pediatric brain tumor research program. The unrestricted funding has given us the freedom over the past year to explore new approaches for the treatment of pediatric medulloblastoma and resulted in the development of a novel drug delivery platform to get drugs past the blood-brain barrier, a major challenge in cancer research. We believe that this nanoparticle delivery system has tremendous potential for the treatment of pediatric brain tumors by utilizing lower drug doses to minimize toxicity, yet maintain or enhance efficacy, and thus improve the lives of children afflicted with cancer.
One of the major issues in pediatric cancer is when a tumor relapses or recurs for which additional treatments often result in additional toxicity to the child, however with minimal benefit in the treatment of the cancer. The continued unrestricted funding through Unravel Pediatric Cancer is allowing us to explore combination drug therapies using our nanoparticle drug delivery system to target the remaining cancer cells that remain after initial radiation and chemotherapy. We are very hopeful that this strategy will allow us to minimize or prevent tumor relapse or recurrence, the worry that every patient and their family has to endure following their initial diagnosis of cancer.
Dr. Marie Bleakley is a pediatric hematologist-oncologist who specializes in hematopoietic (blood-forming) stem cell transplantation for patients with leukemia and other blood cancers.
Her research goal is to develop novel therapies that can optimize the cancer-fighting power of immune T cells while reducing a potentially dangerous side effect known as graft-vs.-host disease, or GVHD.
Dr. Bleakley and her team have already pioneered one novel transplantation approach that selectively removes donor T cells that might cause GVHD. They are also genetically engineering T cell therapies that target unique markers to kill a patient’s cancer cells even more effectively.
Burkitt lymphoma is a highly aggressive cancer which predominantly occurs in children. The treatment for Burkitt lymphoma is high dose, intensive chemotherapy. Although up to 90% of children will be cured with chemotherapy, for children whose disease relapses, the chances of survival are less than 20%. We simply have no good treatment options for these children who slip through the cracks and relapse after chemotherapy. Our lab works to identify novel treatment approaches which may be more effective and less toxic than traditional chemotherapy.
We specifically study the genetics and the biology of Burkitt lymphoma with a focus on changes in the tumor that could be targeted with new therapies. Through generous donations of tumor samples from children with Burkitt lymphoma, we have identified genetic changes in Burkitt lymphoma and that might lead to targeted therapies. One pathway we have studied is targeting a protein called Hsp90. We found that targeting this protein in Burkitt lymphoma cells results in cell death, in part through inhibition of a signaling pathway called PI3K (Giulino-Roth et al, Molecular Cancer Therapeutics, 2017). Inhibitors of PI3K are now being studied in a pediatric clinical trial through the Children’s Oncology Group. This trial includes children with Burkitt lymphoma.
My basic science research has aimed to evaluate new, targeted drugs against pediatric cancers, including the use of combined molecularly-targeted agents against diffuse intrinsic pontine glioma (DIPG). My focus is to translate this work into new treatment options for children with brain and spinal cord tumors.
Dr. Vitanza first became interested in pediatric oncology because it combined both of his passions: working with critically ill children and participating in basic science research. During his pediatric hematology/oncology fellowship at NYU I gained exposure to pediatric neuro-oncology, in which patients are often very ill on presentation, require extensive surgeries, endure prolonged treatment courses, and generally experience poorer outcomes than other pediatric cancer patients. This inspired my focus on children with central nervous system (CNS) tumors.
I continued my clinical and laboratory training during a second fellowship in pediatric neuro-oncology at Stanford University, during which I also worked in Michelle Monje’s Neuroscience and Diffuse Intrinsic Pontine Glioma (DIPG) Lab. In 2016, I joined the faculty at Seattle Children’s Hospital where I care for children with CNS tumors and became an Affiliate Investigator at the Fred Hutchinson Cancer Research Center in the Lab of Jim Olson, MD, PhD, aiming to target DIPG’s molecular aberrations and better understand its immune microenvironment.
Cancer is the most common genetic disorder and affects 1 in 300 children. Cancers are thought to occur as a result of DNA changes that are either inherited or acquired throughout an individual’s lifetime. Advances in sequencing technologies, genome science and bioinformatics finally provide us with the tools to identify these changes and develop precision therapies to attack cancer cells while sparing their normal counterparts. While cancer genomics has entered clinical practice for both pediatric and adult cancer patients, current methods of clinical genomic data analysis are largely limited to the detection of coding mutations, and do not work well for most pediatric cancer patients. To address this, we launched the Treehouse Childhood Cancer Initiative, focusing on the study of tumor RNA as readout of both genetic and epigenetic changes that can drive pediatric tumors. The goal of Treehouse is to increase the number of pediatric cancer patients that benefit from the genomic characterization of their tumor.
We would like to extend our approaches to the study of constitutional genetic diseases, such as structural birth defects. We will use molecular biology, genomic and bioinformatics techniques to understand the etiology of these diseases and identify novel molecular targets for treatment.
I am a pediatric oncologist whose specialty is neuroblastoma. We’ve made significant progress in improving the outlook for many children newly diagnosed with this challenging disease, and we are now able to achieve the best cure rates. For those whose disease returns, we are devising new approaches that are showing encouraging results.
I feel privileged to work as part of a team that sees more patients with neuroblastoma than virtually any other institution. Our exposure to so many patients from so many varied backgrounds and parts of the world affords us an extraordinary amount of experience and knowledge that we draw on each time we meet a new patient. Our team discusses each patient’s unique situation and tailors an individualized plan of care with the greatest chance of success.
We have also learned that in some cases, neuroblastoma disappears on its own, with little or no treatment. We are identifying factors that may predict which patients will experience such spontaneous regression and which patients require more intensive therapy. In addition to patient care and research, I teach fellows and residents.
It is awe-inspiring to see young adults trying to maintain their normal lives while going through cancer treatment. The parents of our patients are also an inspiration; anything we can do for them as doctors and friends is well worth the effort.
Unravel Pediatric Cancer has generously supported the work of Dr. Nai-Kong Cheung, who is studying a vaccine for neuroblastoma as a treatment to prevent relapse of the disease. The vaccine, which was developed at Memorial Sloan Kettering Cancer Center nearly 10 years ago, works by triggering an immune response against the cancer. The MSK-initiated Phase I/II trial for high-risk stage 4 neuroblastoma patients, funded in part by Unravel Pediatric Cancer, has so far accrued nearly 300 patients. The results are highly encouraging—especially in those who had already suffered a relapse of disease prior to entering the study. Recently, the team has initiated the drafting of a new treatment protocol to increase the effectiveness of vaccine therapy. They are also exploring in-depth the impact of a patient’s intestinal flora on his/her immune response during vaccine treatment.
This work would not be possible without friends like Unravel Pediatric Cancer, and we are so grateful for your continued generosity.