Understanding the Science

Weill Cornell Medicine extends our deepest gratitude to the Patrick Bayly Marsano Foundation for making the expanded precision medicine program for pediatric brain tumors a reality.

One of the major road blocks to discovering promising new treatments for children with brain tumors is the lack of tumor tissue and genetic data available. Researchers need to study samples from brain tumors to learn more about them. Without access to tumor tissue, life-saving research would not be possible. Even more importantly, the scientific findings resulting from a donation of this kind may inform the child’s oncology team on potential therapeutic treatment options based on those findings.

Some laboratories, such as the Children’s Brain Tumor Project at Weill Cornell Medicine, already have the tools to collect tumor tissue from a patient and to analyze that tissue through genetic sequencing, bioinformatics, targeted therapy, immunophenotyping, and drug screening. In other words, this enables the research team to study the genetics of the tumor, seek targets based on the presence or absence of genetic mutations, test different drugs against the tumor, and discover unique ways in which the oncology team might be able to treat a child’s brain tumor more effectively.

Tailoring the prevention, diagnosis, and treatment of a patient based on the molecular characteristics of that patient’s disease is known as precision medicine. There are two ways to seek this kind of analysis.

First and most effective, a family can give consent to collect tumor tissue prior to a child undergoing a surgical procedure to remove tumor (biopsy or resection) and that tissue goes from the OR directly to the lab for immediate processing and advanced preservation.

Second, families can request to have tumor tissue sent to laboratories to undergo sequencing at their preferred laboratory. It is important to alert the surgical team of the specific requirements of tissue preservation to ensure the recovery agents used at the lab are compatible.


Genomic sequencing of both DNA and RNA enables our team to identify mutations and/or gene expression alterations, which are the foundation to cancer. Not only is the identification of gene alterations essential to making an accurate diagnosis, but genetic subtypes identified within a particular diagnosis are known to affect an individual’s response to treatment. Ideally, adjustments to treatment can be made accordingly. Information derived from sequencing also enables the scientific team to use targeted drugs when actionable mutations are discovered.

Sequencing isn’t just about identifying mutations that are currently treatable, it is a vehicle for scientific discovery. Identifying mutations in advance means that when researchers do discover a treatment option for a particular mutation, they may be able to apply it to treatment protocols for children who present with the same markers in the future.


Bioinformatics uses advanced computing and mathematics to analyze data, including gene expression or deletion, protein analysis, advanced imaging and clinical annotations, to provide insights into the biology of a tumor helping to expedite progress toward precision medicine. The practice of aggregating and sharing research data to inform scientists is particularly important when considering rare pediatric brain tumors. Powerful new computational research technology, sometimes referred to as “big data,” enables information on rare diseases to be more easily shared and analyzed, resulting in a better understanding of these diseases and how to treat them.


High throughput drug screening is the ability to use automated equipment to rapidly test thousands of different drug compounds for a biological response from the tumor tissue. This allows scientists to identify drugs or a combination of drugs that may have the highest potential efficacy against the patient’s disease.

For example, the Children’s Brain Tumor Project at Weill Cornell is a member of both the Englander Institute of Precision Medicine and Rockefeller University, which are located in close proximity to the lab and have access to more than 300,000 compounds for rapid testing against patient-derived cells generated in our laboratory.

The first step in the process involves in vitro high-throughput drug screening. The team uses chemical libraries to identify drugs, including the most current FDA-approved anticancer drugs, that specifically target gene alterations identified in the patient-specific cells.

Taking it a step further, the patient’s cancer cells may be transplanted into immune-deficient mice to generate an in vivo mouse model that imitates the behavior of the patient tumor from which the cells were derived. These models can then be used to validate the drugs identified in the in vitro screen for their efficacy in vivo. These models will also provide information about the toxicity of the selected drugs or combination of drugs being considered.


Immunophenotyping allows us to understand the immune microenvironment of the tumor, meaning, how the tumor impacts the child’s immune system and how his or her body reacts against the tumor. It is helpful to know which immune cells are present in the tumor microenvironment so the team can identify which specific cells should be targeted. Ideally, treatment can be adapted depending on the immune cells present in the tumor, as well, in order to amplify those immune cells that are effectively fighting the disease.

Our Membership in the Children’s Brain Tumor Network

The Children’s Brain Tumor Network (formerly known as the Children’s Brain Tumor Tissue Consortium) is a central framework where leading experts and institutions work together to solve the challenging problems related to children’s brain tumor research. The CBTN collaborates with the world’s best children’s hospitals, maintains the world’s largest pediatric brain tumor database (including tissue and genomic data), provides open-access, freely-available data for research and supports ground-breaking clinical trials through data-driven precision medicine. The Children’s Brain Tumor Project at Weill Cornell Medicine was one of the original members of the network, and we continue to collaborate on sharing scientific resources to support discoveries into childhood brain and central nervous system (CNS) tumors.


Leaving a Legacy

The diagnosis of an incurable brain tumor is an inconceivable challenge that no child or family should have to face. Tissue donation is vital in the path to changing the prognosis for children facing a similar diagnosis in the future.  Each donation allows us to gain a wealth of invaluable information through molecular, cellular, and genetic analysis of the tissue. It is this information that is so essential to creating a brighter future for the children and families that this disease so greatly affects. The desperate need for tissue samples led us to collaborate with the Gift from a Child initiative, which gathers such samples in what is called a rapid autopsy.