Combination of palbociclib and radiotherapy for glioblastoma

Shane Whittaker, Daniel Madani, Swapna Joshi, Sylvia A. Chung, Terrance Johns, Bryan W Day, Mustafa Khasraw, Kerrie Leanne McDonald

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic.
Original languageEnglish
Article number17033
Number of pages6
JournalCell Death Discovery
Volume3
DOIs
Publication statusPublished - 3 Jul 2017
Externally publishedYes

Cite this

Whittaker, S., Madani, D., Joshi, S., Chung, S. A., Johns, T., Day, B. W., ... McDonald, K. L. (2017). Combination of palbociclib and radiotherapy for glioblastoma. Cell Death Discovery, 3, [17033]. https://doi.org/10.1038/cddiscovery.2017.33
Whittaker, Shane ; Madani, Daniel ; Joshi, Swapna ; Chung, Sylvia A. ; Johns, Terrance ; Day, Bryan W ; Khasraw, Mustafa ; McDonald, Kerrie Leanne. / Combination of palbociclib and radiotherapy for glioblastoma. In: Cell Death Discovery. 2017 ; Vol. 3.
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abstract = "The cyclin-dependent kinase inhibitor, palbociclib has shown compelling efficacy in breast cancer patients. Several pre-clinical studies of glioblastoma (GBM) have also shown palbociclib to be efficacious. In this study, we investigated palbociclib in combination with radiation therapy (RT) for treating GBM. We tested palbociclib (with and without RT) on four patient-derived cell lines (PDCLs; RB1 retained; CDKN2A loss). We investigated the impact of therapy on the cell cycle and apoptosis using flow cytometry, in vitro. Balb/c nude mice were intracranially injected with the PDCL, GBM-L1 and treated orally with palbociclib (with and without RT). Overall survival was measured. Palbociclib treatment resulted in a significant increase in the percentage of cells in the G1 cell cycle phase. Apoptotic cell death, measured by Annexin V was induced. Palbociclib combined with RT acted synergistically with the significant impediment of colony formation. The oral treatment of mice with palbociclib did not show any significant survival advantage when compared to control mice, however when combined with RT, a survival advantage of 8 days was observed. Our results support the use of palbociclib as an adjuvant treatment to RT and warrant translation to the clinic.",
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Whittaker, S, Madani, D, Joshi, S, Chung, SA, Johns, T, Day, BW, Khasraw, M & McDonald, KL 2017, 'Combination of palbociclib and radiotherapy for glioblastoma' Cell Death Discovery, vol. 3, 17033. https://doi.org/10.1038/cddiscovery.2017.33

Combination of palbociclib and radiotherapy for glioblastoma. / Whittaker, Shane; Madani, Daniel; Joshi, Swapna; Chung, Sylvia A.; Johns, Terrance; Day, Bryan W; Khasraw, Mustafa; McDonald, Kerrie Leanne.

In: Cell Death Discovery, Vol. 3, 17033, 03.07.2017.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Madani, Daniel

AU - Joshi, Swapna

AU - Chung, Sylvia A.

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AU - Day, Bryan W

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