We’re committed to showcasing the exceptional work your donation enables — from sponsoring talented physicians and researchers, to supporting pediatric inpatient units and purchasing state-of-the-art equipment. Below is an overview of some of the projects and progress our donors make possible.
Apply for a grant from Pediatric Cancer Foundation for 2020.
(This application is due by Jan 15, 2020 to be considered for our fiscal year 2020-2021.)
PCF Developmental Therapeutics Program (PCFDTP)
RESEARCH LED BY DR. ALICE LEE & DR. STERGIOS ZACHAROULIS
The PCFDTP has become the premier destination for patients and their families in the New York tri-state area who wish access to early phase clinical trials. In 2019, this research will continue their mission to advance new treatments for pediatric cancer through basic science research to define novel therapeutic targets, translational research to adapt observations from the laboratory to patients, and clinical trials participation to bring cutting edge treatments directly to patients. Enrollment to early phase therapeutic trials is a cornerstone of the program and infrastructure funding from the PCF has been instrumental in allowing them to support dedicated research staff to increase accruals to phase I/II trials, facilitate greater scientific contributions to protocol development with consortia and industry partners and further implement pediatric precision cancer medicine program (PIPseq) that uses next-generation sequencing technologies to match patients to genomically-driven experimental therapies.
Clinical Research Pediatric Neuro-Oncology program
RESEARCH LED BY DR. STERGIOS ZACHAROULIS
Investigator-Initiated Trial with Midatech: A phase I study examining the feasibility of intermittent convection-enhanced delivery (CED) of MTX110 for the treatment of children with newly diagnosed diffuse midline gliomas. Diffuse midline gliomas (formally known as diffuse intrinsic pontine glioma-DIPG and bithalamic gliomas) are fatal brain tumors with median survival of 9 months. Many trials with various drugs have failed to show any benefit partly because of inadequate concentration of the drug into the tumor due to the presence of the blood brain barrier (BBB) (a natural barrier that doesn’t allow potentially toxic substances to enter the brain). Collaborated with Professor Gill and Renishaw and to establish a Convection Enhanced Delivery program where using a metallic port connected with 4 catheters inserted in the brain stem, we were able to deliver medicines under controlled steady pressure directly into the pons bypassing BBB in children with diffuse midline tumors. We showed for first time that it is feasible to do that and we had early encouraging results.
Tissue Immune Response, Immunoregulation and Tumor surveillance
Research led by Dr. Erica Fallon
Dr. Fallon’s work focuses on incorporating fundamental studies on mouse models with novel translational approaches on human tissue samples to investigate tissue immune responses, including protective immunity, and compare tissues from pediatric solid tumors to detect differences, investigate mechanism of disease formation, and potentially identify new treatment strategies. They have a unique resource to obtain multiple tissues from research-consented organ donors, enabling novel investigation of human immunity throughout the body over age, disease type, and genetic diversity. They will additionally investigate immunoregulation and tumor surveillance and look to identify focused areas for targeted prevention and/or therapy.
Dr. Lionel Blanc
Dr. Jeff Lipton
Osteosarcomagenesis (OS) in Diamond Blackfan Anemia patients
RESEARCH LED BY DR. JEFFREY LIPTON & DR. LIONEL BLANC
Drs. Lipton and Blanc’s work focuses on understanding how bone cancer develops in patients with a rare genetic disease. Diamond Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by red cell failure, congenital anomalies, poor linear growth and cancer predisposition. The overall goals of this research are (1) to understand the defects in bone development (poor linear growth, osteopenia, skeletal anomalies) as a consequence of RP haploinsufficiency (2) to acquire a fuller understanding of the etiology of OS in the context of DBA, and thus (3) to determine the role of ribosomal protein gene mutations in oncogenesis, using DBA as a model. Recently, their work has been accepted for an oral presentation at the International Society for Pediatric Oncology (SIOP) in Lyon, France in October, 2019. This project has taken almost 5 years to get to this stage. They now have a mouse model that is predisposed to develop osteogenic sarcoma. The next stage of the project is to map out the molecular changes that lead to tumorigenesis in the hope that they can identify molecular targets for therapy. As many know, therapy for osteogenic sarcoma has been stalled with no significant improvements in survival for decades. They are hopeful that this mouse model can be exploited by their group as well as other investigators to improve therapy for this cancer. There is no doubt that without the support of PCF, they would not have been able to accomplish this work. Our contribution will be acknowledged in Lyon.
PCF has been providing support to The Feinstein Institute for Medical Research and Cohen Children’s Medical Center for over 15 consecutive years. The team has garnered major grants from the NIH, DOD and the CDC, all based upon work initially supported by PCF.
Research funded by PCF at The Feinstein Institute has been directed towards studying and understanding Diamond Blackfan anemia.
“Deaths from childhood cancer continue to decrease as researchers at all of the institutions supported by PCF make major strides in our efforts to prevent or cure all of childhood cancer. I look forward to continued support from PCF until we can all declare the battle won!”
– Jeffrey Lipton M.D., Ph.D, Director, Pediatric Hematology/Oncology and Stem Cell Transplantation, Feinstein Institute of Medical Research, Northwell Health Professor of Pediatrics and Molecular Medicine, Hofstra Northwell School of Medicine
Mitchell S. Cairo, MD
Hematological Malignancies Program
RESEARCH LED BY DR. MITCHELL CAIRO
As Chief of Pediatric Hematology, Oncology and Stem Cell Transplantation at Maria Fareri Children’s Hospital, Dr. Mitchell Cairo leads a multidisciplinary team of researchers developing treatments to battle Hematologic Malignancies in children and adolescents through targeted immunotherapies, reduced intensity conditioning and allogeneic stem cell transplantation, novel chemotherapy for reinduction therapy, Human Derived Placental Stem Cell (HDPSC) therapy, haplo identical stem cell transplantation, and single or double umbilical cord blood transplantation in children and adolescents who are at a high risk of Hematological Malignancies. The promise of unlocking treatments by harnessing the power of the patient’s immune system renews the efforts of Dr. Cairo’s team to lead advances that save lives while minimizing unwanted side effects both now and in the future. PCF funding has made possible a Nurse Practitioner Coordinator to support, coordinate, and assist in clinical research.
Overall the program is equipped to design and deliver customized and personalized therapy for each child and adolescent in the cancer center diagnosed with a hematological malignancy.
Specific targeting of protein (mTOR) in Rhabdomysarcoma
RESEARCH LED BY DR. FILEMON DELA CRUZ
Dr. Dela Cruz’s group previously showed that genetic mutations (for example, a mutation in a gene called MYOD1) can contribute to a tumor’s ability to resist chemotherapies, thereby increasing the chances of treatment failure and death from cancer progression in rhabdomyosarcoma (RMS). His team previously examined the genetic mutations of RMS and found that these tumors may rely on specific biological signals to survive. They have performed initial experiments demonstrating that drugs targeting a protein called mTOR may be effective in reducing cell growth in RMS harboring a mutation in the MYOD1 gene.
Dr. Dela Cruz plans to further validate his group’s initial results described above in tumor mouse models to determine if specific targeting of the mTOR protein will be successful in halting tumor growth. The results, if validated further, would provide evidence to support a new way of effectively targeting these tumors that, so far, have resisted commonly used therapies.
Pediatric Hematology/Oncology Fellowship Training Program
RESEARCH LED BY DR. BILL CARROLL AND DR. ELIZABETH ROMAN
Training the next generation of bright, highly-motivated clinician scientists who are dedicated to the practice of patient-centered, compassionate, and research-driven care for children with malignancies and blood disorders. Led by Fellowship Director, Elizabeth Roman, MD, the NYU Langone Pediatric Hematology/ Oncology Fellowship Training Program is a three-year program, accredited by the Accreditation Council for Graduate Medical Education (ACGME), which provides the graduate with comprehensive training in hematology and oncology.
Remarkable strides have been made in the treatment of newly diagnosed pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), yet a subset of children relapse and succumb to therapy-resistant disease. In fact, relapsed leukemia remains a leading cause of cancer-related death in children. Identifying mechanisms of therapy resistance in relapsed leukemia is paramount to developing effective treatments that can overcome these barriers. There have been numerous identified genetic mutations within leukemia cells that can confer intrinsic resistance to chemotherapy agents. However, there are also changes to the environment surrounding the leukemia cells which may also facilitate their pathologic growth and survival. Dr. Robbins will work in the Carroll lab at the NYU Perlmutter Cancer Center, in collaboration with the Aifantis lab, to investigate the “microenvironment” surrounding leukemic cells, in order to identify changes in this niche that may facilitate resistance to both conventional chemotherapy as well as novel immunotherapeutic treatments (e.g. CAR T cells).
Prevention of formation of metastases
Research led by Dr. Jessica Kandel
During the last year, Dr. Kandel’s work expanded their investigations of the effect of the “microbiome” – the bacterial environment contained in our bodies and on our skin. Their findings underscore the realization that this environment significantly impacts children with cancer. Bacterial toxins change the way that blood vessels that feed cancers behave. For example, these molecules can promote blood vessel leakiness that allows cancer cells to escape and circulate, and can also prepare the sites where they will grow as metastases. By dissecting these mechanisms, they are increasingly able to predict how to block and restrain the spread of cancers.
These studies are an important advance, because this is what ultimately causes the loss of children with cancer. This is why they focus on these questions: they seek to prevent the formation of metastases, the distant spread of cancer that is its most deadly form. Their work resulted in important publications this year, and in recognition by the National Cancer Institute that this is a novel and important line of investigation.
Sue Cohn M.D., and Luca Vricella M.D. and Jessica Kandel M.D. – leaders of our new Children’s Surgery, Oncology, and Cardiovascular Service Lines for children. This new collaborative structure reflects a groundbreaking partnership between the University of Chicago and the largest healthcare entity in Illinois, Advocate Aurora, which allows our programs to reach children not only throughout our state but beyond our borders. On this day, we were discussing a novel approach to a very complex case, a child with a tumor involving the lung and heart, which we are collaborating to treat in the most cutting-edge way possible. We would not be able to do this work without the partnership of the Pediatric Cancer Foundation!
Supporting Pediatric Graft-versus-host Disease Research
RESEARCH LED BY DR. JAMES FERRARA & DR. JOHN LEVINE
Bone marrow transplantation or BMT (allogeneic hematopoietic cell transplantation) can cure many hematologic cancers and other childhood blood diseases. Every year, over 1,400 children undergo this lifesaving procedure in the United States and over 5,000 children receive a bone marrow transplant worldwide. Even more children would be able to receive a potentially life-saving bone marrow transplant were it not for the risk of graft-versus-host disease (GVHD), a deadly complication of BMT that develops in 40% of pediatric recipients. GVHD occurs when immune system cells from the bone marrow donor transplanted into the recipient mistake the normal healthy organs as invading foreign cells. When that occurs, the donor immune cells try to destroy the “foreign” tissue as they are programmed to do. Intensive immunosuppression can treat GVHD approximately half of the time. In the remaining cases, the patient either dies or develops a chronic form of the disease which can require years of treatment.
In Mount Sinai Acute GVHD International Consortium (MAGIC), we collect clinical symptom and treatment data weekly to allow us to reconstruct a patient’s clinical course from diagnosis through treatment. MAGIC data coordinators are trained to recognize and question implausible patterns such as significant worsening in GVHD severity without escalation of treatment. As a result of this intensive effort, errors that affect other registries’ data are caught and corrected in the MAGIC database.
MAGIC requires a full-time data coordinator to review, quality assure, curate, and assemble the clinical data on pediatric MAGIC subjects for analysis. We respectfully request the Pediatric Cancer Foundation’s consideration of $75,465 in funding to hire a full-time data coordinator at Mount Sinai, and the opportunity to discuss continued support in subsequent years. This data coordinator would oversee all of the data obtained from pediatric subjects who participate in MAGIC. One year of support will enable us to accomplish our midterm goal to understand the differences in GVHD in children. Ongoing support will help us conduct the research needed to understand and overcome the barriers to optimal health in survivors of pediatric GVHD.
