Originally published on Cornerstone, the CHOP Research Blog.
I edited this article based on a CHOP press release and an additional interview with the investigator.
Pediatric cancer researchers at The Children’s Hospital of Philadelphia believe they have succeeded in their search for a powerful next-generation drug for neuroblastoma tumors with mutations in the anaplastic lymphoma kinase (ALK) gene associated with the cancer. Based on their preclinical findings, they are fast-tracking the launch of a clinical trial this year.
Usually appearing as a solid tumor in the chest or abdomen, neuroblastoma accounts for a disproportionate share of cancer deaths in children, despite many recent improvements in therapy.
The search for better ALK inhibitors originated when, in 2008, CHOP pediatric oncologist Yael Mossé, MD, and colleagues identified ALK mutations as a driver of most cases of rare, inherited neuroblastoma. Subsequent research showed that abnormal ALK changes drive approximately 14 percent of high-risk forms of neuroblastoma.
Based on this knowledge, scientists including Dr. Mossé in the multicenter Children’s Oncology Group were able to repurpose crizotinib, an ALK inhibitor already approved to treat adults with lung cancer, in clinical trials of children with neuroblastoma. But they found that different mutations within the ALK gene in neuroblastoma responded differently to crizotinib, and a mutation labelled F1174L was resistant to the drug.