Anti-tumor effects of rigosertib in high-risk neuroblastoma.

Translational Oncology
Katarzyna RadkeDaniel Bexell

Abstract

High-risk neuroblastoma has a poor prognosis despite intense treatment, demonstrating the need for new therapeutic strategies. Here we evaluated the effects of rigosertib (ON-01910.Na) in preclinical models of high-risk neuroblastoma. Among several hundred cancer cell lines representing 24 tumor types, neuroblastoma was the most sensitive to rigosertib. Treatment of MYCN-amplified neuroblastoma organoids resulted in organoid disintegration, decreased cell viability, and increased apoptotic cell death. Neuroblastoma response to rigosertib involved G2M cell cycle arrest and decreased phosphorylation of AKT (Ser473) and ERK1/2 (Thr202/Tyr204). Rigosertib delayed tumor growth and prolonged survival of mice carrying neuroblastoma MYCN-amplified PDX tumors (median survival: 31 days, treated; 22 days, vehicle) accompanied with increased apoptosis in treated tumors. We further identified vincristine and rigosertib as a potential promising drug combination treatment. Our results show that rigosertib might be a useful therapeutic agent for MYCN-amplified neuroblastomas, especially in combination with existing agents.

References

Mar 16, 2005·Cancer Cell·Kiranmai GumireddyE Premkumar Reddy
Nov 2, 2006·Genome Biology·Anne E CarpenterDavid M Sabatini
Jun 26, 2007·Lancet·John M MarisSusan L Cohn
Oct 29, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Antonio JimenoRoss C Donehower
May 26, 2009·Cancer Chemotherapy and Pharmacology·Amy W ChunManoj Maniar
Jun 19, 2010·The New England Journal of Medicine·John M Maris
Feb 18, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wen Wee MaAntonio Jimeno
Feb 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Colby M ChapmanAdrian Wiestner
May 25, 2013·Nature Reviews. Cancer·Nai-Kong V Cheung, Michael A Dyer
Jun 25, 2013·British Journal of Haematology·Rami S KomrokjiAlan F List
Feb 5, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel W BowlesAntonio Jimeno
Sep 16, 2014·International Journal of Cancer. Journal International Du Cancer·Noémie BraekeveldtDaniel Bexell
Jan 28, 2015·Nature Communications·Linda Holmquist MengelbierDavid Gisselsson
Oct 21, 2015·Cancer Discovery·Brinton Seashore-LudlowStuart L Schreiber
Dec 15, 2015·Nature Chemical Biology·Matthew G ReesStuart L Schreiber
Jan 1, 2015·Computational and Structural Biotechnology Journal·Bhagwan YadavJing Tang
Apr 23, 2016·Cell·Sai Krishna Athuluri-DivakarE Premkumar Reddy
Jun 6, 2018·Nature Genetics·Jenny KarlssonDavid Gisselsson
Sep 13, 2019·Science Translational Medicine·Ann LinJason M Sheltzer
Apr 5, 2020·Nucleic Acids Research·Aleksandr IanevskiTero Aittokallio
Jul 4, 2020·Molecular Cell·Stacey J BakerE Premkumar Reddy
Jul 4, 2020·Molecular Cell·Marco JostJonathan S Weissman
Sep 25, 2020·Science Translational Medicine·Karin HanssonDaniel Bexell

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Apoptosis

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