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Heijkants R, Willekens K, Schoonderwoerd M, et al. Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma. Oncotarget. 2017;9(5):6174-6187doi: 10.18632/oncotarget.23485.
Heijkants, R., Willekens, K., Schoonderwoerd, M., Teunisse, A., Nieveen, M., Radaelli, E., Hawinkels, L., Marine, J. C., & Jochemsen, A. (2018). Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma. Oncotarget, 9(5), 6174-6187. https://doi.org/10.18632/oncotarget.23485
Heijkants, Renier, et al. "Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma." Oncotarget vol. 9,5 (2018): 6174-6187. doi: https://doi.org/10.18632/oncotarget.23485
Heijkants R, Willekens K, Schoonderwoerd M, Teunisse A, Nieveen M, Radaelli E, Hawinkels L, Marine JC, Jochemsen A. Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma. Oncotarget. 2017 Dec 15;9(5):6174-6187. doi: 10.18632/oncotarget.23485. eCollection 2018 Jan 19. PMID: 29464063; PMCID: PMC5814203.
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Oncotarget. 2017 Dec 15;9(5):6174-6187. doi: 10.18632/oncotarget.23485. eCollection 2018 Jan 19.

Combined inhibition of CDK and HDAC as a promising therapeutic strategy for both cutaneous and uveal metastatic melanoma.

Oncotarget

Renier Heijkants, Karen Willekens, Mark Schoonderwoerd, Amina Teunisse, Maaike Nieveen, Enrico Radaelli, Luuk Hawinkels, Jean-Christophe Marine, Aart Jochemsen

Affiliations

  1. Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
  2. Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, Leuven, Belgium.
  3. Department of Oncology, KU Leuven, Leuven, Belgium.
  4. Department of Gastroenterology-Hepatology, Leiden University Medical Center, Leiden, The Netherlands.
  5. Mouse Histopathology Core Facility, VIB Center for the Biology of Disease, KU Leuven, Leuven, Belgium.

PMID: 29464063 PMCID: PMC5814203 DOI: 10.18632/oncotarget.23485

Abstract

Very little to no improvement in overall survival has been seen in patients with advanced non-resectable cutaneous melanoma or metastatic uveal melanoma in decades, highlighting the need for novel therapeutic options. In this study we investigated as a potential novel therapeutic intervention for both cutaneous and uveal melanoma patients a combination of the broad spectrum HDAC inhibitor quisinostat and pan-CDK inhibitor flavopiridol. Both drugs are currently in clinical trials reducing time from bench to bedside. Combining quisinostat and flavopiridol shows a synergistic reduction in cell viability of all melanoma cell lines tested, irrespective of their driver mutations. This synergism was also observed in BRAF

Keywords: CDK; HDAC; apoptosis; metastasized melanoma; synergism

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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