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In a childhood cancer, basic biology offers clues to better treatments
Date:11/9/2011

By studying tumor biology at the molecular level, researchers are gaining a deeper understanding of drug resistance -- and how to avoid it by designing pediatric cancer treatments tailored to specific mutations in a child's DNA. In a fruitful collaboration, pediatric oncologists and biochemists are targeting neuroblastoma, an often-deadly childhood cancer of the peripheral nervous system.

"This scientific study allows us to move ahead in improving drug treatments for children with a particular form of neuroblastoma," said study co-leader Yal P. Moss, M.D., a pediatric oncologist at The Children's Hospital of Philadelphia. Moss teamed up in this research with the study co-leader, Mark A. Lemmon, Ph.D., professor and chair of Biochemistry and Biophysics at the Perelman School of Medicine of the University of Pennsylvania.

"This has been a terrific collaboration," said Lemmon. "We have been working for a long time to understand how growth factor receptors work as signaling 'machines.' With the Moss group, we focused on how control of these receptors is compromised in cancer, and can use the laboratory results to guide directly where to go next in the clinic."

The study appears today in the Nov. 9 issue of Science Translational Medicine.

In neuroblastoma, the most common solid cancer of early childhood, roughly 10 percent of patients have mutations in ALK, the gene carrying the code for the signaling receptor anaplastic lymphoma kinase. Moss, who led a team that discovered this gene's role in 2008, was able to expedite a pediatric clinical trial based on this finding within a year, because an existing ALK inhibitor called crizotinib was already in adult clinical trials for a subset of non-small cell lung cancer patients.

Crizotinib was therefore available for use in a pediatric clinical trial against neuroblastoma, but early results in adult cancers showed that tumors sometimes develop resistance to the drug. The
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Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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