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Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma

Ali Rihani (UGent) , Jo Vandesompele (UGent) , Franki Speleman (UGent) and Tom Van Maerken (UGent)
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Abstract
Background: Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target. Methods: In this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells. Results: Marked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway. Conclusion: Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma.
Keywords
Neuroblastoma, Cell cycle, Palbociclib, Cyclin D1, Targeted therapy, CELL-CYCLE ARREST, KINASE INHIBITOR, TARGET, CANCER, PHOSPHORYLATION, LOCALIZATION, APOPTOSIS, D1

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Citation

Please use this url to cite or link to this publication:

MLA
Rihani, Ali, et al. “Inhibition of CDK4/6 as a Novel Therapeutic Option for Neuroblastoma.” CANCER CELL INTERNATIONAL, vol. 15, 2015.
APA
Rihani, A., Vandesompele, J., Speleman, F., & Van Maerken, T. (2015). Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. CANCER CELL INTERNATIONAL, 15.
Chicago author-date
Rihani, Ali, Jo Vandesompele, Franki Speleman, and Tom Van Maerken. 2015. “Inhibition of CDK4/6 as a Novel Therapeutic Option for Neuroblastoma.” CANCER CELL INTERNATIONAL 15.
Chicago author-date (all authors)
Rihani, Ali, Jo Vandesompele, Franki Speleman, and Tom Van Maerken. 2015. “Inhibition of CDK4/6 as a Novel Therapeutic Option for Neuroblastoma.” CANCER CELL INTERNATIONAL 15.
Vancouver
1.
Rihani A, Vandesompele J, Speleman F, Van Maerken T. Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma. CANCER CELL INTERNATIONAL. 2015;15.
IEEE
[1]
A. Rihani, J. Vandesompele, F. Speleman, and T. Van Maerken, “Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma,” CANCER CELL INTERNATIONAL, vol. 15, 2015.
@article{6972292,
  abstract     = {Background: Neuroblastoma is a neural crest-derived tumor and is the most common cancer in children less than 1 year of age. We hypothesized that aberrations in genes that control the cell cycle could play an important role in the pathogenesis of neuroblastoma and could provide a tractable therapeutic target. 
Methods: In this study, we screened 131 genes involved in cell cycle regulation at different levels by analyzing the effect of siRNA-mediated gene silencing on the proliferation of neuroblastoma cells. 
Results: Marked reductions in neuroblastoma cellular proliferation were recorded after knockdown of CCND1 or PLK1. We next showed that pharmacological inhibition of cyclin D1 dependent kinases 4/6 (CDK4/6) with PD 0332991 (palbociclib) reduced the growth of neuroblastoma cell lines, induced G1 cell cycle arrest, and inhibited the cyclin D1-Rb pathway. 
Conclusion: Selective inhibition of CDK4/6 using palbociclib may provide a new therapeutic option for treating neuroblastoma.},
  articleno    = {76},
  author       = {Rihani, Ali and Vandesompele, Jo and Speleman, Franki and Van Maerken, Tom},
  issn         = {1475-2867},
  journal      = {CANCER CELL INTERNATIONAL},
  keywords     = {Neuroblastoma,Cell cycle,Palbociclib,Cyclin D1,Targeted therapy,CELL-CYCLE ARREST,KINASE INHIBITOR,TARGET,CANCER,PHOSPHORYLATION,LOCALIZATION,APOPTOSIS,D1},
  language     = {eng},
  pages        = {8},
  title        = {Inhibition of CDK4/6 as a novel therapeutic option for neuroblastoma},
  url          = {http://dx.doi.org/10.1186/s12935-015-0224-y},
  volume       = {15},
  year         = {2015},
}

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