Histone Deacetylase Inhibition Has Targeted Clinical Benefit in ARID1A-Mutated Advanced Urothelial Carcinoma.

ABSTRACT: Histone deacetylase (HDAC) inhibition has sporadic clinical efficacy in urothelial carcinoma; the genomic basis for clinical response is not known. In two separate phase I clinical trials testing pharmacokinetic aspects of HDAC inhibitors in advanced solid tumors, we identified one patient with advanced urothelial carcinoma who had a complete response to belinostat, and one patient with advanced urothelial carcinoma who had a partial response to panobinostat. The archived tumors of the responders were genomically characterized in comparison to others with urothelial carcinoma on the trials. Urothelial carcinoma cell lines treated with panobinostat and belinostat were studied to elucidate the mechanisms of benefit. Notably, the urothelial carcinoma tumors that responded to HDAC inhibition h

SUBMITTER: Gupta S 

PROVIDER: S-EPMC6350908 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature