Innovative Research Leading to Drug Discovery – January 2019
Ann & Robert H. Lurie Children’s Hospital of Chicago
Cancer biologist Xiao-Nan Li, MD, Ph.D., Director of Pediatric Xenograft Modeling at the Stanley Manne Children’s Research Institute at Lurie Children’s, has pioneered the development of clinically relevant mouse models of pediatric cancers for drug screening. Specifically, these models are made by taking tumor tissues from patients and implanting them into the anatomic locations in mice reflective of the child’s tumor, where they are tested with specific drugs to determine the best course of therapy. Because the mouse model tumors behave like human tumors, this method produces the most accurate recreation of how tumors in children will respond to specific therapies. With 130 models of different brain tumor subtypes, Dr. Li is recognized as having developed the largest number of tumor models in the world. He is expanding this successful approach to create models for all types of cancers, not only at diagnosis but also at recurrence and at the time of death to better understand tumor invasion and test new drug combinations that can significantly prolong survival times. Our goal is to move to personalized clinical drug screening models that would directly benefit each patient. Cal’s Angels’ support serves as the catalyst to push this important work forward.
Lurie’s Quarterly Impact Update – September 2017
Thank you for your support to accelerate discovery of new oncology therapies for young people treated at Ann & Robert H. Lurie Children’s Hospital of Chicago. Your dedication has been essential as we fully implement our Precision Medicine initiative, including the pending hire of a research technician to expedite research and support the talent and resources we have brought to Lurie Children’s over the last few months.
Lurie Children’s launched its Precision Medicine Initiative in early 2017—an imperative to bring the necessary talent and resources together if we are to find the best therapies that will be most effective against the unique characteristics of each child’s cancer. In recent months, we have made considerable progress in this initiative:
• Our oncology team, together with researchers at our Stanley Manne Children’s Research Institute, are now using an individual’s genetic sequencing and other advanced technologies to analyze biological data, and identify disease biomarkers and potential drug targets. Most tumors arise following mutations in critical genes that lead to uncontrolled cellular growth. In some patients, identifying these genes may aid in tumor diagnosis and define the most appropriate therapy. Other tumors may acquire additional mutations during or following therapy that result in relapse. These examples are just the beginning of what we are now understanding through Precision Medicine. Extensive research is required to identify additional genes that mutate and guide us to target those pathways.
• Our Precision Medicine initiative has also introduced a comprehensive biobanking policy for collecting tissues that are crucial for research, implemented a Predisposition Clinic for patients and families, and recruited critical personnel, including a genetics counselor and a clinical research professional.
As a testament to the growing strength of our research and clinical care, two new globally acclaimed physician-scientists have joined our team. They will provide critical value by developing orthotopic xenograft models (PDX). These orthotopic models are made by taking tumor tissues from patients and implanting them into the anatomic locations in mice reflective of the child’s tumor, where they are tested with specific drugs to determine the best course of therapy. This method is difficult to conduct, but produces the most accurate recreation of how tumors in children will respond to drugs.
• Oren Becher, MD, recently came from Duke University School of Medicine and has established his laboratory. Dr. Becher has extensive experience developing models of pediatric brain tumors, particularly Diffuse Intrinsic Pontine Glioma. These models enable us to study genes and mutations that influence cancer development and evaluate novel therapies that could translate into new clinical trials for children. His work will also be informed by the range of clinical trials available at Lurie Children’s and the multi-institution trials we participate in.
• Xiao-Nan Li, MD, PhD, will join our program from Baylor University Texas Children’s Hospital in January 2018. His team will develop animal models in all pediatric cancers, not only at diagnosis, but also at recurrence and at the time of death. Dr. Li’s team includes Research Assistant Professor Xingding Zhang, PhD, who joined our faculty in late spring to establish Dr. Li’s lab and transfer cell lines and breeding colonies from Baylor to Lurie Children’s to begin drug screening of molecular-targeted agents.
Your funding will bring a vital link to our oncology team by allowing these transformational initiatives and world-class investigators to speed up research and ultimately bring better therapies to children sooner. I look forward to updating you on our progress as we continue our search for a research technician with the right skill set to partner with these scientists.
Lurie’s Quarterly Impact Update – June 2017
We remain deeply grateful for Cal’s Angels’ leadership gift to the Division of Hematology, Oncology, Neuro-Oncology and Stem Cell Transplantation at Ann & Robert H. Lurie Children’s Hospital of Chicago. Your support will accelerate our efforts in pediatric drug discovery, making it possible to bring new therapies from the laboratory to human clinical trials in a more efficient and cost-effective way. As the focus of pediatric cancer research shifts to precision medicine and the development of targeted therapies based on the molecular signatures of specific types of cancer, rather than the site of origin, the work made possible through your support promises to pave the way for less toxic and more individualized therapies that will improve outcomes for our patients and all children with cancer.
Specifically, we plan to utilize a portion of your $525,000 investment to hire a new research technician to support pre-clinical laboratory studies of new drug compounds. It will also cover costs associated with acquiring various therapies for testing, including molecularly targeted therapies that form the foundation of Lurie Children’s new Precision Medicine Initiative.
Launched earlier this year, Lurie Children’s Precision Medicine Initiative is revealing insights into the biological, environmental and lifestyle factors affecting each child’s disease and using them to create individually tailored treatment plans. Working in close alignment with investigators at the Stanley Manne Children’s Research Institute, our oncology team will use genetic sequencing and other advanced technologies to analyze biological data and identify biomarkers of disease and potential drug targets. Patients will receive personalized recommendations for treatment according to the assessment of their tumor. Information from each child will be fed back into the lab to fuel discovery of increasingly more precise diagnostics and therapies. Our research teams will use laboratory models to study new drug combinations and solve the significant problem of drug resistance that limit the effectiveness of cancer therapies. As we gather data from increasingly larger numbers of patients who undergo advanced sequencing, this will inform new research questions that will form the basis for future studies to develop more targeted and effective treatments. The impact of our Precision Medicine Initiative will be felt across the spectrum of cancer care – from early diagnosis and treatment to strategies to improve long-term outcomes.
Fueling New Collaborations
Significant resources are needed to advance drug discovery in pediatric oncology. Your gift provides crucial funding to recruit a research technician who will partner with investigators across the Stanley Manne Children’s Research Institute as well as Northwestern University Feinberg School of Medicine. The ideal candidate will have a chemistry background and experience partnering with the pharmaceutical industry to acquire compounds for single and/or combination testing in established mouse models. Examples of two studies that will benefit from the research technician’s support include:
•Rintaro Hashizume, MD, PhD, has created an animal model to examine the effectiveness of delivering various chemotherapy agents intranasally to children with aggressive brain tumors, particularly diffuse intrinsic pontine glioma (DIPG), which has a very poor survival rate. Dr. Hashizume’s goal is to complete pre-clinical therapeutic testing in the next 3-5 years and then proceed to clinical trials.
•In January, world renowned researcher Oren Becher, MD, officially joined Lurie Children’s from Duke University. Dr. Becher has extensive experience developing novel mouse models of pediatric brain tumors. He has developed a genetically engineered mouse model of DIPG that faithfully replicates the human disease in children and represents an important platform with which to study the biology of DIPG and evaluate new therapeutics.
The addition of a new research technician will speed efforts to develop clinical trials and increasingly more effective therapies.
Improved diagnoses, earlier interventions and superior outcomes. These are the promises to our patients and families that drive all that we do at Lurie Children’s. Today, we are closer than ever to achieving our vision. Cal’s Angel’s investment will be a powerful catalyst to accelerate research discovery and transform the lives of children.
Announcement: Cal’s Angels funds Lurie Children’s groundbreaking children’s cancer research
Cal’s Angels partners with Lurie Children’s Hospital and Northwestern University Feinberg School of Medicine to create new treatments for children’s cancers and save more children’s lives!
Although significant advances in care and research have been achieved over the last half-century, cure rates for certain forms of childhood cancers have seen little to no improvement. Moreover, aggressive therapies currently used to treat these cancers can lead to life-long complications such as learning disabilities, heart disease, secondary cancers, and more.
While the need to develop safer, more effective therapies has never been greater, this comes at a time when there is a growing crisis in pediatric drug discovery as fewer new drugs are being developed and approved for use in children. The pharmaceutical industry has approximately 900 adult cancer drugs in the development pipeline and almost none for children’s cancers. The development and testing of new agents for pediatric populations has been hit particularly hard because the diseases that affect children are different, have a smaller potential market, pose greater regulatory obstacles and offer a limited return on investment. As a result, there is a critical imperative for the medical community to initiate, develop and evaluate new therapies specifically formulated for children and adolescents.
Cal’s Angels and Lurie Children’s are committed to moving research forward as quickly as possible to save more children’s lives. Working collaboratively with researchers at Northwestern University Feinberg School of Medicine, Lurie Children’s will initiate a drug discover program, sponsored by Cal’s Angels, for the repurposing of existing drug compounds and ongoing testing of new medications. Specifically, the program will use patient derived xenografts – where a sample of a child’s own cancer, either bone marrow or solid tumor, is used to grow a tumor in mice – to speed development of less toxic and more effective therapies for pediatric cancer in a more cost effective and efficient way. Accountability and quarterly reporting will occur throughout the trial.
Find out how you can be a part of this groundbreaking research and help save the lives of children with cancer.
Lurie’s Quarterly Impact Update – December 2017
As we start a new year, I would like to express my appreciation for the support and thoughtfulness Cal’s All-Star Angel Foundation has demonstrated in order to provide brighter futures for children and their families. Your investment is enabling us to obtain the necessary personnel and resources to pursue breakthrough research that will produce increasingly more individualized and effective treatments for our patients.
Early in the coming year, we will begin the search for a skilled research technician to coincide with the arrival of internationally recognized cancer biologist Xiao-Nan Li, MD, PhD. As you may recall from our last report, Dr. Li will assume the new role of Director of Pediatric Xenograft Modeling at the Stanley Manne Children’s Research Institute in January. He is a world leader in creating novel mouse models, called patient-derived orthotopic xenograft (PDOX) models, for preclinical drug screening and biological studies of pediatric tumors. Dr. Li actively participates in National Cancer Institute-sponsored research consortia, including serving as Chair of the High Grade Glioma Committee of the Pediatric Brain Tumor Consortium. His expertise and substantial research funding will allow us to advance our Precision Medicine initiative. The pending hire of a research technician will help to accelerate the work of this accomplished investigator and bring the most effective personalized drug combinations to patients at a rapid pace.
I am pleased to share that our first joint project with Dr. Li is already in the planning stages. This project aims to develop PDOX models from surgical samples of various types of pediatric brain tumors obtained from patients treated at Lurie Children’s and Texas Children’s Hospital. The PDOX models will faithfully replicate the biology of recurrent brain tumors and provide us with a much-needed and ample supply of recurrent tumor tissues for detailed genomic analysis to understand mechanisms of therapy resistance and identify new targets. Mice bearing recurrent brain tumors will be ready-made for testing novel drug combinations. Our ultimate aim is to secure certification for this novel system so that preclinical drug testing results can be applied to guide clinical treatment of children with malignant brain tumors.
Research has the best potential to transform pediatric health care and ultimately, to improve children’s lives. Your partnership is invaluable to our work. I look forward to updating you on our progress as we begin our search for a research technician. I would be pleased to arrange for members of Cal’s Angels to meet with Dr. Li and tour his laboratory once he settles in to his new role. Feel free to contact T.J. Johnson, Assistant Vice-President of Major Gifts, at firstname.lastname@example.org or (312) 227-7251.
With deepest gratitude,
Stewart Goldman, MD
Division Head, Hematology, Oncology, Neuro-Oncology & Stem Cell Transplantation
Meryl Suzanne Weiss Distinguished Professor in Hematology, Oncology and Stem Cell Transplantation
Professor of Pediatrics, Northwestern University Feinberg School of Medicine
Director, Center for Clinical Trials Research
Co-director, Falk Brain Tumor Center, Stanley Manne Children’s Research Institute