The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis

• DOI: 10.1038/s41419-020-02986-w
• Publication Date: 2020-09-17T21:38:34Z
• Authors: Laia París-Coderch; Aroa Soriano; Carlos Jiménez; Tatiana Erazo; Pau Muñoz-Guardiola; Marc Masanas; Roberta Antonelli; Ariadna Boloix; José Alfón; Héctor Pérez-Montoyo; Marc Yeste-Velasco; Carles Domènech; Josep Roma; Josep Sánchez de ...; Lucas Moreno; José M. Lizcano; Soledad Gallego; Miguel F. Segura
• Keywords: Drug development; Antineoplastic Agents; Apoptosis; Endoplasmic Reticulum; Article; Paediatric cancer; Inhibitory Concentration 50; Mice; Neuroblastoma; 03 medical and health sciences; Drug Development; Cell Line, Tumor; Autophagy; Animals; Humans; Isotretinoin; Cell Proliferation; 0303 health sciences; Endoplasmic Reticulum Stress; 3. Good health; Pancreatic Neoplasms; Linoleic Acids; Unfolded Protein Response; Female; Neoplasm Transplantation; DNA Damage

Neuroblastoma is the leading cause of cancer death in children aged 1 to 4 years. Particularly, five-year overall survival for high-risk neuroblastoma below 50% with no curative options when refractory or relapsed. Most current therapies target cell division and proliferation, thereby inducing DNA damage programmed death. However, aggressive tumours often present alterations these processes are resistant therapy. Therefore, exploring alternative pathways induce tumour will provide new therapeutic opportunities patients. In this study we aimed at testing potential ABTL0812, a novel anticancer drug that induces cytotoxic autophagy eliminate cells, which currently phase II clinical trials adult tumours. Here, show ABTL0812 impaired viability representative lines regardless genetic associated bad prognosis resistance Oral administration mice bearing xenografts growth. Furthermore, our findings revealed that, neuroblastoma, induced via induction endoplasmic reticulum stress, activation unfolded protein response, apoptosis. Remarkably, potentiated antitumour activity chemotherapies differentiating agents such as irinotecan 13-cis-retinoic acid. conclusion, distinctive mechanism action makes it standout be used alone combination