Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma

Research output: Contribution to journalArticle


title = "Anti-tumor effects of PIM/PI3K/mTOR triple kinase inhibitor IBL-302 in neuroblastoma",
abstract = "The PI3K pathway is a major driver of cancer progression. However, clinical resistance to PI3K inhibition is common. IBL-302 is a novel highly specific triple PIM, PI3K, and mTOR inhibitor. Screening IBL-302 in over 700 cell lines representing 47 tumor types identified neuroblastoma as a strong candidate for PIM/PI3K/mTOR inhibition. IBL-302 was more effective than single PI3K inhibition in vitro, and IBL-302 treatment of neuroblastoma patient-derived xenograft (PDX) cells induced apoptosis, differentiated tumor cells, and decreased N-Myc protein levels. IBL-302 further enhanced the effect of the common cytotoxic chemotherapies cisplatin, doxorubicin, and etoposide. Global genome, proteome, and phospho-proteome analyses identified crucial biological processes, including cell motility and apoptosis, targeted by IBL-302 treatment. While IBL-302 treatment alone reduced tumor growth in vivo, combination therapy with low-dose cisplatin inhibited neuroblastoma PDX growth. Complementing conventional chemotherapy treatment with PIM/PI3K/mTOR inhibition has the potential to improve clinical outcomes and reduce severe late effects in children with high-risk neuroblastoma.",
keywords = "cisplatin, IBL-302, multikinase inhibition, neuroblastoma, PI3K",
author = "Sofie Mohlin and Karin Hansson and Katarzyna Radke and Sonia Martinez and Carmen Blanco-Apiricio and Cristian Garcia-Ruiz and Charlotte Welinder and Javanshir Esfandyari and Michael O'Neill and Joaquin Pastor and {von Stedingk}, Kristoffer and Daniel Bexell",
year = "2019",
month = aug,
day = "1",
doi = "10.15252/emmm.201810058",
language = "English",
volume = "11",
journal = "EMBO Molecular Medicine",
issn = "1757-4684",
publisher = "Federation of European Neuroscience Societies and Blackwell Publishing Ltd",
number = "8",