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

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^V600E mutant melanoma that had acquired resistance to BRAF inhibit

SUBMITTER: Heijkants R 

PROVIDER: S-EPMC5814203 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature