831 Proteasome inhibitor functional profiling in CTCL

Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin that presents with skin manifestations and often incurable at advanced stages blood involvement. Genomic profiling of malignant cells from CTCL patients has revealed diverse range genetic mutations underlying the disease, including single nucleotide gene copy number alterations involving JAK/STAT NF-κB signaling pathways. Synergistic drug combination treatment in may allow for targeting multiple aberrant pathways while minimizing toxicity single-agent resistance. Proteasome inhibitors have been used to treat other hematologic malignancies act through mechanisms induce cancer cell death, suppression activation. We previously reported JAK1/2 inhibitor ruxolitinib synergistically potentiates cytotoxic effect bortezomib, first-generation reversible proteasome inhibitor, primary lines. are currently investigating first second-generation different subunit selectivity their therapeutic potential as agents BCL2, HDAC, BET, or JAK we identified having CTCL. Our vitro viability assays shown similar sensitivity lines bortezomib well such oprozomib IC50 values double-digit nanomolar range. Preliminary data using show varying degrees synergy Chou-Talalay method when tested patient-derived cells. These screenings provide methodology strategic assessment useful reference exploration