Neuroblastoma is not necessarily a highly malignant disease; in some cases the tumors remain localized and often can shrink without any therapy. The tumors that are malignant have an assortment of mutations: gene amplifications or deletions that affect the proliferative activity of the cell.
The mutations associated with the aggressive form of neuroblastoma can be combined in many different ways, conferring upon each child with neuroblastoma a unique genetic profile. Given the heterogeneity in genetic profile from patient to patient, it is understandable that some treatments work for some patients and some do not.
Genetic profile-targeted intervention — rather than blanket treatment for all neuroblastoma patients — has the potential to increase cure rates.
Researchers at the Center for Childhood Cancer Research, including John M. Maris, MD, are helming the Therapeutically Applicable Research to Generate Effect Treatments (TARGET) initiative to match specific tumor mutations to new therapies. This has been shown to be very promising in adult cancers.
Research is progressing toward developing patient-specific “bar codes” created through genetic technology, sequencing technology, and proteomics, allowing for individualized therapy based upon the genetic profile of the patient. Small molecular therapies (kinase inhibitors) targeting patient-specific drivers of malignancy mediated by oncogenic proteins can then be administered, resulting in better outcomes and higher cure rates for children with neuroblastoma. This approach is also applicable to the rationale selection of new immune therapies.