Scientists at St. Jude Children's Research Hospital have achieved a groundbreaking success in treating a pediatric patient with high-risk refractory neuroblastoma using targeted therapy guided by clinical genomics.

The St. Jude team utilized germline DNA and RNA sequencing to identify therapeutic vulnerabilities in the patient's cancer, leading to a tailored treatment approach.

The treatment specifically targeted a genetic vulnerability caused by a mutation in the BARD1 gene, which resulted in a defect in the DNA damage repair pathway.

Oncologists adapted the treatment to incorporate the PARP inhibitor talazoparib alongside irinotecan, with talazoparib already having FDA approval for adult use.

This combination of PARP inhibition and chemotherapeutics effectively targeted the cancer's DNA damage repair defect, leading to the destruction of the malignancy.

Following the identification of the BARD1 mutation, the patient experienced a dramatic clinical response, remaining disease-free for over two years without further therapy.

Dr. Sara Federico, co-corresponding author of the study, noted that multiple therapies had previously failed the patient before the BARD1 mutation was identified.

Refractory neuroblastoma is known for resisting conventional treatments and is associated with a poor prognosis, making this case particularly significant.

This case sets a precedent for targeting DNA damage response gene vulnerabilities in solid tumors, potentially benefiting other patients with similar genetic mutations.

The findings from this case were published in the New England Journal of Medicine, underscoring its importance in the field of pediatric oncology.

Dr. Jinghui Zhang emphasized the critical role of understanding the genetic basis of cancer in achieving positive clinical outcomes.