The Role and Therapeutic Implication of HDAC8 in Neuroblastoma

Neuroblastoma lineage arises from a neural crest origin and is a typically common tumor among the pediatric population. Survival rate for this disease has improved over the years, however, patients with MYCN amplification correlate with a poor prognosis, warranting improved therapies. The utility and efficacy of pan-HDAC inhibitors for the treatment for various solid tumors has increased with promising results. Isoform-specific HDAC inhibitors have been developed to improve the therapeutic window and reduce side effects. The role of isoform-specific HDAC inhibitors, namely HDAC8 inhibitors, has recently been investigated in numerous tumor histologies, including neuroblastoma, among other neural crest-derived tumors. Long term pan-HDAC inhibition has been demonstrated to induce differentiation and regression to a benign-like phenotype in neuroblastoma in vivo. HDAC8 inhibition has been shown to inhibit growth and induce differentiation in neuroblastoma cells. The role of HDAC8 inhibition on neuroblastoma and regression of the disease merits further investigation.