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Dong J, Park SY, Nguyen N, et al. The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells. Oncotarget. 2018;9(12):10497-10509doi: 10.18632/oncotarget.24041.
Dong, J., Park, S. Y., Nguyen, N., Ezhilarasan, R., Martinez-Ledesma, E., Wu, S., Henry, V., Piao, Y., Tiao, N., Brunell, D., Stephan, C., Verhaak, R., Sulman, E., Balasubramaniyan, V., & de Groot, J. F. (2018). The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells. Oncotarget, 9(12), 10497-10509. https://doi.org/10.18632/oncotarget.24041
Dong, Jianwen, et al. "The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells." Oncotarget vol. 9,12 (2018): 10497-10509. doi: https://doi.org/10.18632/oncotarget.24041
Dong J, Park SY, Nguyen N, Ezhilarasan R, Martinez-Ledesma E, Wu S, Henry V, Piao Y, Tiao N, Brunell D, Stephan C, Verhaak R, Sulman E, Balasubramaniyan V, de Groot JF. The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells. Oncotarget. 2018 Jan 08;9(12):10497-10509. doi: 10.18632/oncotarget.24041. eCollection 2018 Feb 13. PMID: 29535822; PMCID: PMC5828226.
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Oncotarget. 2018 Jan 08;9(12):10497-10509. doi: 10.18632/oncotarget.24041. eCollection 2018 Feb 13.

The polo-like kinase 1 inhibitor volasertib synergistically increases radiation efficacy in glioma stem cells.

Oncotarget

Jianwen Dong, Soon Young Park, Nghi Nguyen, Ravesanker Ezhilarasan, Emmanuel Martinez-Ledesma, Shaofang Wu, Verlene Henry, Yuji Piao, Ningyi Tiao, David Brunell, Clifford Stephan, Roel Verhaak, Erik Sulman, Veerakumar Balasubramaniyan, John F de Groot

Affiliations

  1. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  2. Institute of Biosciences and Technology, Texas A&M Health Science Center at Houston, Center for Translational Cancer Research, Houston, TX, USA.
  3. Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  4. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  5. Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  6. The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

PMID: 29535822 PMCID: PMC5828226 DOI: 10.18632/oncotarget.24041

Abstract

BACKGROUND: Despite the availability of hundreds of cancer drugs, there is insufficient data on the efficacy of these drugs on the extremely heterogeneous tumor cell populations of glioblastoma (GBM).

RESULTS: The PKIS of 357 compounds was initially evaluated in 15 different GSC lines which then led to a more focused screening of the 21 most highly active compounds in 11 unique GSC lines using HTS screening for cell viability. We further validated the HTS result with the second-generation PLK1 inhibitor volasertib as a single agent and in combination with ionizing radiation (IR).

CONCLUSIONS: Our results reinforce the potential therapeutic efficacy of volasertib in combination with radiation for the treatment of GBM.

METHODS: We used high-throughput screening (HTS) to identify drugs, out of 357 compounds in the published Protein Kinase Inhibitor Set, with the greatest efficacy against a panel of glioma stem cells (GSCs), which are representative of the classic cancer genome atlas (TCGA) molecular subtypes.

Keywords: glioblastoma; polo-like kinase 1; radiation; sensitization; volasertib

Conflict of interest statement

CONFLICTS OF INTEREST John de Groot is consulting/advisory board member for Genentech, Novartis, Celldex, VBL Therapeutics, Celldex, Deciphera Pharmaceuticals and MundiPharma.

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