sbi-0206965 and Neuroblastoma

Neuroblastoma is the most common extracranial solid malignancy in the pediatric population, accounting for over 9% of all cancer-related deaths in children. Autophagy is a cell self-protective mechanism that promotes tumor cell growth and survival, making it an attractive target for treating cancer. However, the role of autophagy in neuroblastoma tumor growth and metastasis is largely undefined. Here we demonstrate that targeted inhibition of an essential autophagy kinase, unc-51 like autophagy kinase 1 (ULK1), with a recently developed small-molecule inhibitor of ULK1, SBI-0206965, significantly reduces cell growth and promotes apoptosis in SK-N-AS, SH-SY5Y, and SK-N-DZ neuroblastoma cell lines. Furthermore, inhibition of ULK1 by a dominant-negative mutant of ULK1 (dnULK1

Topics: Animals; Apoptosis; Autophagy-Related Protein-1 Homolog; Benzamides; Cell Line, Tumor; Cell Proliferation; Humans; Intracellular Signaling Peptides and Proteins; Mice, Inbred NOD; Mice, SCID; Neoplasm Metastasis; Neuroblastoma; Pyrimidines; TNF-Related Apoptosis-Inducing Ligand; Topoisomerase Inhibitors; TOR Serine-Threonine Kinases; Xenograft Model Antitumor Assays