Federal Grant Award Summary

The National Cancer Institute awarded Children's Research Institute a Project Grant of $467,968 under the Cancer Treatment Research program (CFDA 93.395) to conduct research evaluating the synergistic therapeutic effects of retinoic acid and proteasome inhibitors in neuroblastoma treatment. The grant period runs from June 1, 2026 through May 31, 2028. The primary deliverable is a systematic evaluation of combination therapy approaches using three proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) combined with isotretinoin (13-cis-retinoic acid) across genetically diverse neuroblastoma models that recapitulate key clinical biomarkers including MYCN amplification, TP53 mutations, and ALK status.

The research utilizes both in vitro cell lines and patient-derived xenografts, with preclinical validation conducted through live vertebrate animal models approved by the Children's Research Institute's Institutional Animal Care and Use Committee. The work aims to validate whether proteasome inhibitors can potentiate retinoic acid therapy by enhancing differentiation and apoptosis in high-risk neuroblastoma patients, whose current 5-year survival rates remain limited at 40-50% despite intensive multimodal therapy. The project addresses a critical clinical need to overcome retinoic acid resistance and develop novel combination strategies for improved pediatric cancer treatment outcomes.