The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

Anti-tumor effects of rigosertib in high-risk neuroblastoma

Author

  • Katarzyna Radke
  • Karin Hansson
  • Jonas Sjölund
  • Magdalena Wolska
  • Jenny Karlsson
  • Javanshir Esfandyari
  • Kristian Pietras
  • Kristina Aaltonen
  • David Gisselsson
  • Daniel Bexell

Summary, in English

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.

Department/s

  • Division of Translational Cancer Research
  • Molecular Pediatric Oncology
  • LUCC: Lund University Cancer Centre
  • Experimental oncology
  • Division of Clinical Genetics
  • Pathways of cancer cell evolution

Publishing year

2021-08

Language

English

Publication/Series

Translational Oncology

Volume

14

Issue

8

Document type

Journal article

Publisher

Neoplasia Press

Topic

  • Cancer and Oncology

Keywords

  • Neuroblastoma
  • ON-01910
  • ON-01910.Na
  • Patient-derived xenografts
  • Rigosertib

Status

Published

Research group

  • Molecular Pediatric Oncology
  • Experimental oncology
  • Pathways of cancer cell evolution

ISBN/ISSN/Other

  • ISSN: 1936-5233