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Inherited Childhood Cancers

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A Riley Children’s Health researcher is working alongside national collaborators to seek new treatments for inherited childhood cancers. Under an $11.4 million grant from the National Cancer Institute, initially awarded in 2015, Dr. Wade Clapp, chairman of the Department of Pediatrics at Indiana University School of Medicine and physician-in-chief at Riley Children’s will spearhead the investigation.

The Specialized Programs of Research Excellence (SPORE) grant is co-piloted by Kevin Shannon, MD, professor of pediatrics at the University of California, San Francisco. He, Dr. Clapp and other national institutions will investigate tumors that develop in neurofibromatosis type 1 (NF1), a genetic disorder that is the most common precursor to pediatric cancer.

“Our SPORE grant is distinguished by its strong childhood cancer focus and multi-institutional effort, which brings together a coalition of the best NF1 investigators in the United States and likely the world,” Dr. Clapp said. “The grant involves six major institutions and the Pediatric Oncology Branch of the National Cancer Institute. The number of children with these genetic diseases is relatively small, so this sort of structure allows us to get the trials done efficiently and expediently.”

With nearly 100,000 individuals living with NF1 in the U.S., patients with the syndrome have a higher risk of developing specific benign tumors and cancers such as brain tumors, leukemia and tumors that progress into sarcomas. Among these cancers, the Ras protein, a key signaling protein involved in more than a third of cancers, is interrupted by the NF1 gene and becomes lost in tumors with NF1 mutations. This leading-edge research, though, will reverse this disruption and lead to new therapies for many cancers, according to Dr. Clapp.

“Our SPORE team applies data generated in the laboratory to guide the development of innovative clinical trials,” Dr. Shannon said. “This new NCI grant will allow us to extend this ground-breaking work that is evaluating a number of promising treatments for decreasing abnormal Ras signaling.”

“In the past five years, the group has completed a series of basic studies and clinical trials that have led to the first-ever FDA drug approval for NF1 and successful trials that are encouraging for new treatments in peripheral nerve tumors and myeloid leukemia,” Dr. Clapp added. “In this renewal, we are building on that work as well as initiating a new project focused on brain tumors that occur at higher rates in adolescents and young adults with NF1.”

Additionally, the grant – also known as the Developmental and Hyperactive Ras Tumor (DHART) SPORE – is the only one of 63 SPORE grants in the country to particularly focus on childhood cancers. It includes a Developmental Research Program and a Career Enhancement Program, providing funds to investigators to contribute to the ongoing NF1 study. There are currently three research projects underway to move the analysis forward.

“The groundbreaking work done by this group in this SPORE has already been paradigm and practice-changing and has fundamentally impacted patients in the most positive ways,” Kelvin Lee, MD said, director of the IU Health Simon Cancer Center. “I believe the advances by Dr. Clapp and his team are only going to accelerate with this renewal.”

Pediatric hematologists and oncologists at Riley Children’s combine breakthrough research with comprehensive care to support inherited childhood cancers and more.



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Designated as Best Children's Hospitals by U.S. News & World Report, Ranked in 10 Specialties in 2020-21

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Find adult services at iuhealth.org


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