Integrative discovery of treatments for high-risk neuroblastoma
- Almstedt, E., Elgendy, R., Hekmati, N., Rosén, E., Wärn, C., Olsen, T.K., Dyberg, C., Doroszko, M., Larsson, I., Sundström, A., Arsenian Henriksson, M., Påhlman, S., Bexell, D., Vanlandewijck, M., Kogner, P., Jörnsten, R., Krona, C., Nelander, S.
- Nature communications 11: 71 (Journal)
- Registered Authors
- MeSH Terms
- Antineoplastic Agents/administration & dosage*
- Cell Line, Tumor
- Drug Evaluation, Preclinical
- Mice, Nude
- Mitogen-Activated Protein Kinase 8/antagonists & inhibitors
- Mitogen-Activated Protein Kinase 8/genetics
- Mitogen-Activated Protein Kinase 8/metabolism
- Neuroblastoma/drug therapy*
- Receptor, Cannabinoid, CB2/antagonists & inhibitors
- Receptor, Cannabinoid, CB2/genetics
- Receptor, Cannabinoid, CB2/metabolism
- Xenograft Model Antitumor Assays
- 31900415 Full text @ Nat. Commun.
Almstedt, E., Elgendy, R., Hekmati, N., Rosén, E., Wärn, C., Olsen, T.K., Dyberg, C., Doroszko, M., Larsson, I., Sundström, A., Arsenian Henriksson, M., Påhlman, S., Bexell, D., Vanlandewijck, M., Kogner, P., Jörnsten, R., Krona, C., Nelander, S. (2020) Integrative discovery of treatments for high-risk neuroblastoma. Nature communications. 11:71.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes