Researchers at the Children’s Hospital of Philadelphia (CHOP) have highlighted the potential of anaplastic lymphoma kinase (ALK) inhibition therapy in treating hereditary neuroblastoma, a rare form of childhood cancer. The findings, published in JCO Precision Oncology, suggest that this approach could establish a new standard of care.
Despite advancements in treating high-risk neuroblastoma, the five-year survival rate remains below 50%. Yael P. Mossé, MD, a senior study author and Professor of Pediatrics at CHOP’s Cancer Center, noted that most familial cases are linked to the ALK mutation. This mutation can be tested for and directly targeted. In their case report, Mossé focused on a mother and daughter both diagnosed with neuroblastoma carrying the ALK R1275Q mutation. They achieved long-term remission with targeted ALK inhibitors.
“Our research marks a major advancement in precision medicine for patients predisposed to hereditary neuroblastoma,” said Mossé. “With these findings, we can offer new hope for affected families and pave the way for more personalized, less invasive treatment strategies in pediatric oncology.”
The study demonstrated that small molecule ALK inhibitors could be more effectively used for hereditary cases than initially developed sporadic neuroblastoma cases with non-inherited mutations. The daughter was diagnosed at six months old and responded dramatically to crizotinib after standard chemotherapy and surgery failed her when her cancer recurred.
The mother was diagnosed at 36 years old with bilateral adrenal tumors during pregnancy five years later. After delivering a healthy baby, she began crizotinib treatment but switched to alectinib due to side effects. Following surgical removal of the tumors, she continued alectinib treatment and has maintained remission for several years. Both undergo semiannual surveillance with whole-body MRI and circulating tumor DNA (ctDNA) testing without evidence of disease recurrence.
The authors recommend ALK inhibitors as frontline therapy for patients with inherited mutations, potentially reducing intensive chemotherapy and surgery needs. They emphasize lifelong monitoring’s importance, challenging current guidelines that end surveillance in childhood. Researchers plan to study whether people with hereditary ALK have a lower risk of developing drug resistance than those with non-inherited mutations.
The research received support from Alex’s Lemonade Stand Foundation, Patricia Brophy Endowed Chair in Neuroblastoma Research, and National Cancer Institute (NCI) R35 CA220500.
Mossé et al., “Anaplastic Lymphoma Kinase Inhibition Therapy for Hereditary Neuroblastoma.” JCO Precis Onc., Online April 28, 2025. DOI: 10.1200/PO-24-00886.
