Childhood Cancer

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Rhabdoid Tumor

Rhabdoid tumor is a rare tumor that commonly starts in the kidneys, but can also begin in the liver or other soft tissues of the body. It can also begin in the brain, where it is known as AT/RT. The disease can spread to other parts of the body.  Rhabdoid tumors are most often diagnosed in infants and toddlers.

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Rhabdoid Tumor Heroes

Latest Rhabdoid Tumor blog posts

July 9, 2018

by Trish Adkins

In 2000, the first draft of the map of human genome—a mosaic representation of characteristics of what makes our biology uniquely human—was released. The map paved the way for more genomics research in several fields ranging from human biology to agriculture and gave scientists models of genetically normal cells which they could compare to abnormal cells, like those cells that make childhood cancer so deadly.

Now, in 2018, an ALSF funded-research project has resulted in the release of over 270 genetic sequences of 25 different types of childhood cancer used routinely by the National Cancer Institute’s Pediatric Preclinical Testing Consortium (PPTC). Each unique tumor model and its biological characteristic data is available to all academically qualified petitioners—opening the door for breakthroughs in childhood cancer research.

Keep reading to learn how cures are getting closer, one childhood cancer genome at a time. 

The story behind the 270 models begins with the PPTC

Founded in 2015 and funded by the National Cancer Institute, the consortium works to develop reliable preclinical testing data for potential pediatric cancer drugs. There are hundreds, maybe thousands of potential cancer drugs—making the study of each drug in a pediatric clinical trial impossible. The PPTC narrows down the list, providing researchers with reliable drug effectiveness data that they can use to accelerate research from “bench to bedside;” bringing science out of the lab and into the clinic. The models studied are directly derived from childhood cancers at diagnosis or relapse, and thus are directly representative of the types of cancers treated in clinical trials.

However, while there is a large pool of potential drugs, there was not a large pool of accurate pediatric tumor models for which to test the drugs. This has long been a struggle for the pediatric oncology research community. Over 14.1 million people are diagnosed with cancer each year worldwide, but only 250,000 of those cases are pediatric cancer. The pool of potential tumors to model is small and obtaining viable tumor cells is difficult, especially for some types of pediatric cancers like spinal cord tumors where securing tissue samples is tricky because of the tumor’s location. 

The PPTC had an idea for a new major effort, the Pediatric Preclinical Genomic Characterization Project, which sought to characterize the tumor samples being used in drug testing. These patient-derived xenograft (PDX) childhood cancer models were being used routinely, but the majority did not have detailed genetic data available. 

The potential was enormous: with a critical mass of PDX models made available to the scientific community, the PPTC could accelerate the route to clinical trials much more rapidly than ever before, bringing potentially lifesaving treatment to children waiting desperately for cures.

There was one catch: there was no funding available for a PDX sequencing project. That’s when ALSF entered the picture. 

The Foundation learned about the PPTC and its desire to generate high-quality PDX genetic data to streamline science’s understanding of why novel treatments work in some cases, but do not work in others, and immediately recognized its promise. 

“ALSF has a legacy of filling critical research and family services gaps in the childhood cancer community,” said Liz Scott, Co-Executive Director of ALSF.  “We knew that funding the PPTC’s genomic sequencing project had the potential to spark long-lasting impact, collaborative efforts and ultimately advance the pace of finding cures for all kids with cancer.”

Legacies of Hope
With the ALSF funding, the PPTC could characterize the stored samples that had been donated by children battling pediatric cancer. Some donations came while a child was in treatment, with an institution’s requested permission to use extra tumor tissue that was not needed for diagnosis or treatment protocol, for research.  

Other donations came from families eager to find cures even when it was too late for their own child. These profound gifts, given at the time of death, left behind a legacy of hope waiting to be unlocked.  

The PPTC has access to over 400 samples representing 25 different types of childhood cancer, stored at -80℃ in its five locations at institutions in the United States and also in Australia, and continues to generate more, often in collaboration with Dr. Patrick Reynolds who receives ALSF funding for the Childhood Cancer Repository where many genetic models are generated. The vast majority of the samples represent relapsed disease and have the promise of modeling childhood cancers at the time that many new investigational treatments are tried in the clinic in Phase 1 trials.

While the PPTC could have tried to establish the tumor lines in a test tube or dish, the researchers leading the project knew from prior experience that growing tumors in artificial environments could lead to the generation of different mutations in revolt to their new homes. These mutations would lead to inauthentic cell lines and muddy the search for drugs that could work. 


Accelerating the Clinical Trial Process
Bringing the right drugs to the clinic has long been a struggle for pediatric oncology researchers.  

The first priority is to ensure a patient’s safety in a clinical trial by adhering to specific safeguards before the trial begins and during the trial. But a safe drug is not necessarily effective and can offer false hope to patients who are enrolled in clinical trials after one relapse—or several.  

Using the PDX models, researchers could discover the “good drugs”—the drugs most likely to be safe and effective in killing cancer cells, and also discover the “bad drugs”—those that are not effective and those that might even result in resistant disease.

The models also give researchers the opportunity to continue to move away from treating diseases by name and begin treating the specific genetic lesions that might drive cancer growth. It is the literal meaning of “killing two birds with one stone”— two different types of cancers may share a genetic trait and in turn, could be sensitive to the same drug. 

“With good models, we can begin designing experiments more robustly and begin getting the right drugs to the clinic and to children quickly,” said Dr. John Maris, MD, of ALSF’s Scientific Advisory Board and Children’s Hospital of Philadelphia’s neuroblastoma representative in the PPTC.

ALSF’s contribution allowed the PPTC, in collaboration with Baylor College of Medicine and Nationwide Children’s Hospital (led by David Wheeler and Julie Gastier-Foster), to genomically characterize over 270 PDX models with four different genomic tools—each tool giving researchers more clues to how the genes and proteins drive cancer growth.

Researchers worked to filter out any noise or irregularities in the final data, using existing cancer cell knowledge and past research. They have ensured the models matched their cells of origin and have retained known cancer driver mutations over time. 

The PPTC began using the data immediately—fulfilling its mission of matching drugs to genetic targets and testing in advance of human clinical trials. 

Now, eighteen months after the PPTC commenced the PDX project, other scientists now have the same opportunity. The data, which was released on July 9, 2018, is available to all academically qualified petitioners through the PedcBioPortal for Childhood Cancer Genomics (pedcBio portal). Raw characterization data will be available on the database of Genotypes and Phenotypes (dbGaP) in the coming months. Tissue samples will be available by request—for just the cost of postage to ship. 

“When childhood cancer relapses, it can become lethal,” said Dr. Maris. “But today, the scientific community has open access to deep genetic profiling that will help overcome some of the major problems we have when treating childhood cancer. We’ve now accelerated years ahead in our search for cures.”

Read more about the PPTC project, as well as other innovative ALSF research here. 

December 19, 2017

The process of bringing an idea from the lab to clinical trial can take years. Researchers are not only required to prove the effectiveness of their science, they also need to get FDA approval to provide an experimental therapy to actual patients. On top of all this, researchers also must ensure that their home hospital has the correct infrastructure in place to administer a clinical trial.

Over 700 new children are affected by cancer every day. For these kids, years are too long to wait. To help researchers get to the clinical trial phase quicker, ALSF established the Reach grants. The program, which awards multi-year grants annually, accelerates researchers closer to clinical trial. 

This year’s grantees are embracing cutting-edge trends in cancer research and working towards cures for kids battling some of the deadliest cancers. Meet our 2017 Reach grantees:

1. Dr. Gianpietro Dotti and Dr. Barbara Savoldo, University of North Carolina 

In August, the FDA approved CAR T cell immunotherapy as a standard of care for some types of relapsed leukemia. T cells, an essential part of the immune system, are collected from patients and then modified, so when they are returned to the body, they find leukemia cells and kill them. 

However, the potential of CAR T cell immunotherapy as a cure for different types of cancer does not stop there. CAR T cells have also been shown to kill glioblastoma (GBM) cells in the lab.

Dr. Dotti and Dr. Savoldo are developing a similar strategy as a potential treatment for GBM, a type of brain tumor that is notoriously hard to eliminate surgically or with chemotherapy and radiation. 

Dr. Dotti’s team has found that CAR T cells kill the majority of GBM tumor cells, but some GBM cells survive by blocking the altered T cell. Now, the team is working to make the CAR T cells unable to be blocked by GBM cells. The hope is this research will lead to a major breakthrough for children battling GBM, providing a treatment option with minimal side effects. 

Dr. Dotti’s work is co-funded with Bear Necessities Pediatric Cancer Foundation.

2. Dr. Michael Burke and  Dr. Jeffrey Medin, Children’s Hospital of Wisconsin

Acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. AML progresses quickly and about half of all children relapse. Relapsed AML has a dismal survival rate—the need for treatments is urgent. 

Dr. Burke and Dr. Medin are studying the use of oncolytic virotherapy as a treatment for AML. Oncolytic virotherapy uses altered virus cells that are injected into cancer cells. The infected cancer cells can be seen by the immune system, which then goes to work to kill cancer and rid the body of infection. 

Dr. Burke and Dr. Medin take a small number of leukemia cells from a patient and infect those cells with a virus outside of the body. The virus then tricks leukemia cells into making a protein called interleukin 12 (IL-12). When IL-12 cells are returned to the patient’s body, their immune system sees the infected cells and begins attacking the leukemia cells. 

A similar approach has been successfully used with adults battling relapsed AML. If successful, this approach would not only provide a treatment option to children with relapsed disease, but also provide an alternative to intensive chemotherapy and the side effects associated with current AML treatment. 

3. Dr. Alex Kentsis, Memorial Sloan-Kettering Cancer Center

The causes of genetic mutations that lead to the development of cancer are still poorly understood. This is particularly true for solid tumors of children and young adults that express the PGBD5 mutation. This mutation is expressed in several solid tumors, including rhabdoid tumors, lethal tumors that can develop in any part of the body including the lungs, kidneys, brain, liver and soft tissues. 

Dr. Kentsis recently identified that the PGBD5 mutation causes the genes to rearrange and leads to the development of cancer. This phenomenon is called genomic rearrangement and is common in a majority of childhood solid tumors. Dr. Kentsis hopes that his study will lead to the development of a new therapeutic strategy to inhibit the rearrangement and move directly to the clinical trial phase, providing improved therapeutic options for children battling solid tumors. 

ALSF began the Reach grant program in 2013. Read more about our Reach grant projects here