Anti-tumor effects of rigosertib in high-risk neuroblastoma
(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.
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- author
- Radke, Katarzyna LU ; Hansson, Karin LU ; Sjölund, Jonas LU ; Wolska, Magdalena ; Karlsson, Jenny LU ; Esfandyari, Javanshir LU ; Pietras, Kristian LU ; Aaltonen, Kristina LU ; Gisselsson, David LU and Bexell, Daniel LU
- organization
- publishing date
- 2021-08
- 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}}, }