romidepsin + bortezomib

Romidepsin + bortezomib is an **investigational combination therapy** consisting of romidepsin, a histone deacetylase inhibitor (HDAC inhibitor), and bortezomib, a proteasome inhibitor. This combination has been studied primarily in hematologic malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), B-cell lymphoma, T-cell lymphoma, peripheral T-cell lymphoma (PTCL), and cutaneous T-cell lymphoma (CTCL). Romidepsin induces apoptosis through histone deacetylase inhibition, impacting gene expression and cell cycle, while bortezomib induces cell death by inhibiting the 26S proteasome, leading to the accumulation of ubiquitinated proteins and cell cycle arrest. The combination is mechanistically synergistic: bortezomib blocks romidepsin-induced NF-κB activation, resulting in downregulation of the antiapoptotic proteins Bcl-xL and XIAP, reduced p100 to p52 processing (alternative NF-κB pathway), and increased pro-apoptotic protein Bim, promoting caspase-driven apoptosis. Clinical studies report modest activity and safety profiles similar to the single agents. It is not approved as a combination and remains investigational[1][2][3][5][7].