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Anti-tumor effects of rigosertib in high-risk neuroblastoma

Radke, Katarzyna (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Hansson, Karin (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups
Sjölund, Jonas (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups
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Wolska, Magdalena (author)
Lund University
Karlsson, Jenny (author)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments
Esfandyari, Javanshir (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups
Pietras, Kristian (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Experimentell onkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Experimental oncology,Lund University Research Groups
Aaltonen, Kristina (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups
Gisselsson, David (author)
Lund University,Lunds universitet,Avdelningen för klinisk genetik,Institutionen för laboratoriemedicin,Medicinska fakulteten,Cancercellers evolution,Forskargrupper vid Lunds universitet,Division of Clinical Genetics,Department of Laboratory Medicine,Faculty of Medicine,Pathways of cancer cell evolution,Lund University Research Groups,Skåne University Hospital
Bexell, Daniel (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Molekylär barnonkologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Molecular Pediatric Oncology,Lund University Research Groups
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 (creator_code:org_t)
Elsevier BV, 2021
2021
English.
In: Translational Oncology. - : Elsevier BV. - 1936-5233. ; 14:8
Related links:
http://dx.doi.org/10... (free)
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https://doi.org/10.1...
https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Keyword

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

Publication and Content Type

art (subject category)
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