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CancerScope A lthough scientists have made great strides in applying breakthroughs in precision medicine to many adult cancers, the same cannot be said of pediatric diseases. However, researchers, advocates, and lawmakers are hoping to bridge the divide, largely by identifying more opportunities to include children, adolescents, and young adults in precision oncology clinical trials. Exactly why pediatric precision oncology has experienced fewer research gains is a varied and complicated issue, according to experts. Nonetheless, Katherine Janeway, MD, a senior physician and director of clinical genomics at the Dana-Farber Cancer Institute and Children’s Hospital in Boston, Massachusetts, points to several important drivers of the disparity. She co-authored an article in a March 2019 special edition of Science that outlined problems and possibilities in the field.1 First, although pediatric cancers remain the second leading cause of death in children aged 1 to 14 years, they are considered rare and tend not to receive as much attention and research funding as more common cancers. Approximately 11,060 children in the United States are projected to have been diagnosed with the disease in 2019,2 which accounts for less than 1% of all cancers, according to the American Cancer Society. “It is a greater challenge to fully characterize rare diseases because you need to sequence a large number of each rare pediatric cancer to fully characterize the genome,” Dr. Janeway says. Second, she says, to validate the use of a specific drug against a certain cancer type with a particular biomarker characteristic, researchers must develop models of those subtypes. In turn, the models must get into the hands of the pharmaceutical industry, which then would take the lead in drug development. “We haven’t had as many validated preclinical models, which are primarily cell lines and mouse models, in the right place at the right time,” she says. Furthermore, pharmaceutical interest has long been unreliable, with the industry viewing drug development for pediatric cancers as unprofitable. Indeed, although approximately 900 drugs are in the pipeline for adult cancers, only a few are in development for children, according to Kids v Cancer, a nonprofit advocacy organization. Lastly, some of the more common genomic events in pediatric cancers are harder to target. According to Dr. Janeway, many pediatric cancers are characterized by canonical transcription factor gene fusions, which can be challenging to treat with current precision therapies. Despite these barriers, Dr. Janeway and others have seen progress on a variety of fronts. One is the regulatory landscape. To spur improvements in drug development, Congress passed the Research to Accelerate Cures and Equity for Children (RACE) Act in 2017; it goes into effect this year. Although not a new law, the RACE Act updates the Pediatric Research Equity Act (PREA), which was approved in 2003. PREA gives the US Food and Drug Administration (FDA) the authority to require that pharmaceutical companies conduct pediatric studies for drugs already under review for adult indications. According to Kids v Cancer, PREA has not been applied to cancer because children’s cancers often originate in different parts of the body from adult cancers. What is more, PREA requirements were typically waived for cancer drugs that had been designated as orphan drugs by the FDA. (The FDA Orphan Drug Designation program provides orphan status to drugs and biologics that are intended for the treatment, diagnosis, or prevention of rare diseases affecting fewer than 200,000 people in the US.) The RACE Act ensures that cancer drugs with orphan disease designations will no longer be exempt. The ultimate goal, of course, is to increase pediatric oncologists’ access to novel therapies, with the potential of helping their patients live longer. Moreover, the act gives the FDA the authority to require that any new cancer drug be studied in pediatric cancers for which the molecular target of the drug is relevant. That Citing hurdles in clinical trial recruitment and drug development, researchers are exploring ways to close gaps Precision Medicine for Pediatric Cancers Lags Behind That for Adult Cancers