Classification of Gene Mutations in a Children's Cancer May Point to Improved Treatments

Oncology researchers studying gene mutations in the childhood cancer neuroblastoma are refining their diagnostic tools to predict which patients are more likely to respond to drugs called ALK inhibitors that target such mutations. Removing some of the guesswork in diagnosis and treatment, the researchers say, may lead to more successful outcomes for children with this often-deadly cancer.

“Some mutations are more important than others,” said Yaël P. Mossé, MD, a pediatric oncologist at The Children’s Hospital of Philadelphia, and a co-leader of the new study published online today in the journal Cancer Cell. “By integrating biochemistry into our clinical strategies, we can better match a patient’s specific ALK-mutation profile with an optimum treatment.” Mossé is also an assistant professor of Pediatrics in the Perelman School of Medicine, University of Pennsylvania.

“Understanding the specific mutations that trigger signals in cell receptors to stimulate cell growth will help us identify biomarkers for specific subtypes of neuroblastoma,” said study co-leader Mark A. Lemmon, PhD, professor and chair of Biochemistry and Biophysics at Penn. Lemmon’s research focuses on cell receptors in cancer.

Mossé, Lemmon and their computational collaborator Ravi Radhakrishnan, PhD, an associate professor in the department of Bioengineering at Penn, say their new findings will provide crucial data for a pivotal phase 3 study for patients with ALK-driven high-risk neuroblastoma. This trial will be conducted through the Children’s Oncology Group (COG), a cooperative research organization encompassing over 250 pediatric cancer programs in North America. The COG is supported by the National Cancer Institute.

A solid tumor of the peripheral nervous system, often appearing in the chest or abdomen, neuroblastoma is the most common cancer in infants. It accounts for a disproportionate share of cancer deaths in children, with cure rates lagging behind those for other pediatric cancers.

The current study concentrates on various mutations in ALK, the anaplastic lymphoma kinase gene. Mossé led a team that first discovered in 2008 that an ALK mutation caused a hereditary form of neuroblastoma, and also identified ALK mutations implicated in some non-hereditary neuroblastoma.

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