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Children's Hospital of Philadelphia Researchers Recommend New Standard of Care for Families with Hereditary Neuroblastoma Linked to ALK Mutation

New approach could update treatment and monitoring protocols

, /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) highlighted the success of anaplastic lymphoma kinase (ALK) inhibition therapy in treating hereditary neuroblastoma, a rare subset of a common childhood cancer. Researchers suggest that the findings, published recently in JCO Precision Oncology, could help establish a new standard of care.

Despite significant advances in the treatment of high-risk neuroblastoma, the 5-year survival rate after diagnosis remains less than 50%. However, Yael P. Mossé, MD, a senior study author and a Professor of Pediatrics in CHOP's Cancer Center, and her team have previously found that most familial cases are linked to the ALK mutation, which can be tested for and directly targeted. In this case report, Mossé focused on a mother and daughter who were both diagnosed with neuroblastoma and carried the ALK R1275Q mutation, demonstrating how 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."

In the study, researchers demonstrated that small molecule ALK inhibitors, initially developed for sporadic neuroblastoma with non-inherited ALK mutations, could be even more effectively implemented for hereditary cases. The daughter was diagnosed with neuroblastoma at six months old and following standard chemotherapy and surgery that failed her, she responded dramatically to the ALK inhibitor, crizotinib, after her cancer recurred.

The mother, who had been asymptomatic, was diagnosed at 36 years old with bilateral adrenal tumors during a pregnancy five years later. After delivering a healthy baby, she began crizotinib, later switching to a different ALK inhibitor, alectinib, due to side effects. Following surgical removal of the tumors, the mother continued alectinib treatment and has maintained remission several years. Both the mother and daughter undergo semiannual surveillance with whole-body MRI and circulating tumor DNA (ctDNA) testing with no evidence of disease recurrence.

The authors say the report could change how hereditary neuroblastoma for patients with an ALK mutation is treated and followed. They recommend ALK inhibitors as a frontline therapy for patients with the inherited mutations, potentially reducing the need for intensive chemotherapy and surgery. They also stress the importance of lifelong monitoring, challenging current guidelines that end surveillance in childhood. Next, the 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 was supported by 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.

About Children's Hospital of Philadelphia:
A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey. CHOP also operates the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia, the Behavioral Health and Crisis Center (including a 24/7 Crisis Response Center) and the Center for Advanced Behavioral Healthcare, a mental health outpatient facility. Its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit https://www.chop.edu.