Discovery of epi-Enprioline as a Novel Drug for the Treatment of Vincristine Resistant Neuroblastoma

Abstract

Neuroblastoma is a childhood solid tumour originating from undifferentiated neural progenitor cells of the sympathetic nervous system. Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. In the present study, we aimed to identify novel drugs that can inhibit the growth and survival of chemoresistant neuroblastoma. High-throughput screening identified a small molecule, epi-enprioline that was able to induce apoptosis of vincristine-resistant neuroblastoma cells via the mitochondrial apoptotic pathway. Epi-enprioline reduced tumour growth in multiple preclinical models, including an orthotopic neuroblastoma patient-derived xenograft model in vivo. In summary, our data suggest that epi-enprioline can be considered as a lead compound for the treatment of vincristine-resistant neuroblastoma uncovering a novel strategy, which can be further explored as a treatment for drug-resistant neuroblastoma.

Investigation of chemoresistance to first-line chemotherapy and its possible association with autophagy in high-risk neuroblastoma

“…Several previous studies focused on overcoming NB resistance to improve the antitumor efficacy ( 9 , 21 , 23 , 24 ). Increasing the dose of chemotherapy but ensuring that the dose is still within the safe range to reduce the occurrence of chemoresistance is one of the primary solutions ( 25 ).…”