A new therapy might help treat a rare, high-risk cancer that begins development in the fetus or embryo, neuroblastoma, according to recent results from cell culture experiments. Neuroblastoma tumors express high levels of a gene called MYCN, and MYCN levels correlate with poor prognosis. Less than half of children with high-risk neuroblastoma survive.1

This study, published in Cancer Cell, examined data from a large drug screen to predict the B-cell lymphoma 2 (BCL-2) inhibitor ABT-199 targeted MYCN-amplified neuroblastomas. In subsequent cell culture models of neuroblastoma, ABT-199 indeed decreased neuroblastoma proliferation by inhibiting BCL-2. Researchers also found another investigational drug, the Aurora Kinase A inhibitor MLN8237, enhanced ABT-199 in both cell cultures and an advanced mouse model.

By inhibiting BCL-2, ABT-199 caused neuroblastoma cells to die in a process called apoptosis. ABT-199 was specific to neuroblastoma cells with high levels of MYCN. This specificity was due to the cellular increase of a protein that promotes apoptosis, NOXA. Perhaps surprisingly, MYCN, which usually promotes proliferative tumor growth, could be used to increase NOXA levels, thereby increasing tumor cell death.

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MLN8237 enhanced ABT-199’s antitumor activity by further deregulating the BCL-2 family of proteins, which are proteins that regulate apoptosis. In both single ABT-199 treatment and combined ABT-199 and MLN8237 treatment, neuroblastoma cells with amplified MYCN were specifically targeted.

“The positive preclinical activity and safety profile of this targeted therapy combination will hopefully set the stage for clinical trials in a subset of neuroblastoma patients who urgently need new, more effective therapies,” stated Anthony Faber, PhD, assistant professor at the Philips Institute for Oral Health Research at the Virginia Commonwealth University School of Dentistry and a member of the Developmental Therapeutics research program at Virginia Commonwealth University Massey Cancer Center, Richmond.

ABT-199 is currently being evaluated in clinical trials for a different disease.


1. Ham J, Costa C, Sano R, et al. Exploitation of the apoptosis-primed state of MYCN-amplified neuroblastoma to develop a potent and specific targeted therapy combination. Cancer Cell. 2016;29(2):159-172. doi:10.1016/j.ccell.2016.01.002.