Integrative Genomic and Immunogenomic Analysis of Neuroblastoma

Background:

Most patients having high-risk neuroblastoma (NBL)--primarily a childhood cancer--do not achieve long-term survival and eventually succumb to an incurable disease recurrence. Further, the limited involvement of pharmaceutical companies and small patient cohorts hinder the development of new drugs for pediatric cancers.

Recently, immunotherapies that harness the patient's own immune system to fight cancer have emerged as a promising approach to treat tumors. Of these, adoptive T-cell therapies are the only regimen known to produce cures in heavily pretreated metastatic melanoma patients. This approach has not yet been applied in patients having high-risk NBL.

Project Goal:

We will explore whether tumor and normal DNA sequence (genome) data collected from high-risk NBL patients can be used to identify targets for adoptive T-cell therapies in this group. Through genomic analysis, we aim to identify patients whose immune system can mount an effective response against cancer.

While adoptive T-cell therapies have cured patients having metastatic melanoma, most patients with high-risk NBL will likely require a combination of different treatments. Therefore, to accompany our immunotherapy analysis, we will aggregate and computationally analyze genomic data from a large number of NBL patients to identify situations where subsets of NBL patients could benefit from adult cancer drugs, based on the similarity of their genomes. Despite differences in the biology of tumors that affect adults and children, pediatric cancer patients have benefited from targeted therapies developed for adult tumors. Such findings may identify new treatment leads that result in timely translation of the discoveries to clinical trials.