Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Anti-tumor effects of rigosertib in high-risk neuroblastoma

Radke, Katarzyna LU ; Hansson, Karin LU ; Sjölund, Jonas LU ; Wolska, Magdalena ; Karlsson, Jenny LU ; Esfandyari, Javanshir LU ; Pietras, Kristian LU orcid ; Aaltonen, Kristina LU ; Gisselsson, David LU and Bexell, Daniel LU (2021) In Translational Oncology 14(8).
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Neuroblastoma, ON-01910, ON-01910.Na, Patient-derived xenografts, Rigosertib
in
Translational Oncology
volume
14
issue
8
article number
101149
publisher
Neoplasia Press
external identifiers
  • scopus:85107706780
  • pmid:34118691
ISSN
1936-5233
DOI
10.1016/j.tranon.2021.101149
language
English
LU publication?
yes
id
82a74a74-571a-4a77-96e2-33b2e80f4ba1
date added to LUP
2021-07-06 11:01:20
date last changed
2024-06-16 15:55:18
@article{82a74a74-571a-4a77-96e2-33b2e80f4ba1,
  abstract     = {{<p>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.</p>}},
  author       = {{Radke, Katarzyna and Hansson, Karin and Sjölund, Jonas and Wolska, Magdalena and Karlsson, Jenny and Esfandyari, Javanshir and Pietras, Kristian and Aaltonen, Kristina and Gisselsson, David and Bexell, Daniel}},
  issn         = {{1936-5233}},
  keywords     = {{Neuroblastoma; ON-01910; ON-01910.Na; Patient-derived xenografts; Rigosertib}},
  language     = {{eng}},
  number       = {{8}},
  publisher    = {{Neoplasia Press}},
  series       = {{Translational Oncology}},
  title        = {{Anti-tumor effects of rigosertib in high-risk neuroblastoma}},
  url          = {{http://dx.doi.org/10.1016/j.tranon.2021.101149}},
  doi          = {{10.1016/j.tranon.2021.101149}},
  volume       = {{14}},
  year         = {{2021}},
}