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Integrative discovery of treatments for high-risk neuroblastoma

Almstedt, Elin ; Elgendy, Ramy ; Hekmati, Neda ; Rosén, Emil ; Wärn, Caroline ; Olsen, Thale Kristin ; Dyberg, Cecilia ; Doroszko, Milena ; Larsson, Ida and Sundström, Anders , et al. (2020) In Nature Communications 11.
Abstract

Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk... (More)

Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
11
article number
71
publisher
Nature Publishing Group
external identifiers
  • scopus:85077479931
  • pmid:31900415
ISSN
2041-1723
DOI
10.1038/s41467-019-13817-8
language
English
LU publication?
yes
id
14af58c2-76d0-44db-9287-bc7b7db80798
date added to LUP
2020-01-21 17:05:15
date last changed
2024-04-17 02:20:38
@article{14af58c2-76d0-44db-9287-bc7b7db80798,
  abstract     = {{<p>Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.</p>}},
  author       = {{Almstedt, Elin and Elgendy, Ramy and Hekmati, Neda and Rosén, Emil and Wärn, Caroline and Olsen, Thale Kristin and Dyberg, Cecilia and Doroszko, Milena and Larsson, Ida and Sundström, Anders and Arsenian Henriksson, Marie and Påhlman, Sven and Bexell, Daniel and Vanlandewijck, Michael and Kogner, Per and Jörnsten, Rebecka and Krona, Cecilia and Nelander, Sven}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{01}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Integrative discovery of treatments for high-risk neuroblastoma}},
  url          = {{http://dx.doi.org/10.1038/s41467-019-13817-8}},
  doi          = {{10.1038/s41467-019-13817-8}},
  volume       = {{11}},
  year         = {{2020}},
}