Integrative discovery of treatments for high-risk neuroblastoma

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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; Sundström, Anders; Arsenian Henriksson, Marie; Påhlman, Sven; Bexell, Daniel; Vanlandewijck, Michael; Kogner, Per; Jörnsten, Rebecka; Krona, Cecilia; Nelander, Sven.

In: Nature Communications, Vol. 11, 71, 03.01.2020.

Research output: Contribution to journalArticle

Harvard

Almstedt, E, Elgendy, R, Hekmati, N, Rosén, E, Wärn, C, Olsen, TK, 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, vol. 11, 71. https://doi.org/10.1038/s41467-019-13817-8

APA

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]. https://doi.org/10.1038/s41467-019-13817-8

CBE

Almstedt E, Elgendy R, Hekmati N, Rosén E, Wärn C, Olsen TK, 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:Article 71. https://doi.org/10.1038/s41467-019-13817-8

MLA

Vancouver

Almstedt E, Elgendy R, Hekmati N, Rosén E, Wärn C, Olsen TK et al. Integrative discovery of treatments for high-risk neuroblastoma. Nature Communications. 2020 Jan 3;11. 71. https://doi.org/10.1038/s41467-019-13817-8

Author

Almstedt, Elin ; Elgendy, Ramy ; Hekmati, Neda ; Rosén, Emil ; Wärn, Caroline ; Olsen, Thale Kristin ; Dyberg, Cecilia ; Doroszko, Milena ; Larsson, Ida ; Sundström, Anders ; Arsenian Henriksson, Marie ; Påhlman, Sven ; Bexell, Daniel ; Vanlandewijck, Michael ; Kogner, Per ; Jörnsten, Rebecka ; Krona, Cecilia ; Nelander, Sven. / Integrative discovery of treatments for high-risk neuroblastoma. In: Nature Communications. 2020 ; Vol. 11.

RIS

TY - JOUR

T1 - Integrative discovery of treatments for high-risk neuroblastoma

AU - Almstedt, Elin

AU - Elgendy, Ramy

AU - Hekmati, Neda

AU - Rosén, Emil

AU - Wärn, Caroline

AU - Olsen, Thale Kristin

AU - Dyberg, Cecilia

AU - Doroszko, Milena

AU - Larsson, Ida

AU - Sundström, Anders

AU - Arsenian Henriksson, Marie

AU - Påhlman, Sven

AU - Bexell, Daniel

AU - Vanlandewijck, Michael

AU - Kogner, Per

AU - Jörnsten, Rebecka

AU - Krona, Cecilia

AU - Nelander, Sven

PY - 2020/1/3

Y1 - 2020/1/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85077479931&partnerID=8YFLogxK

U2 - 10.1038/s41467-019-13817-8

DO - 10.1038/s41467-019-13817-8

M3 - Article

C2 - 31900415

AN - SCOPUS:85077479931

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 71

ER -