trametinib + quisinostat

Trametinib + quisinostat is an experimental all-small-molecule combination of the MEK1/2 inhibitor trametinib and the second-generation pan–histone deacetylase (HDAC) inhibitor quisinostat, investigated preclinically as a strategy to enhance antitumor activity and overcome resistance to MAPK-pathway–targeted therapies. Trametinib selectively inhibits MEK1/2 in the RAS–RAF–MEK–ERK signaling cascade, thereby reducing ERK phosphorylation and tumor cell proliferation, while quisinostat potently inhibits multiple HDAC isoforms, including HDAC4, leading to increased histone acetylation, altered transcriptional programs, and promotion of tumor cell death.[3] Preclinical work in BAP1‑mutant uveal melanoma identified quisinostat as a highly active HDAC inhibitor and showed that combining it with trametinib produced at least additive cytotoxic effects in vitro, supporting further exploration of MEK plus HDAC blockade in solid tumors harboring MAPK pathway activation and epigenetic vulnerabilities.[3][2]