bortezomib + arsenic trioxide

Bortezomib + arsenic trioxide is an investigational combination therapy consisting of two small molecule drugs with distinct but complementary mechanisms of action. Bortezomib is a proteasome inhibitor that disrupts protein degradation pathways, leading to cell cycle arrest and apoptosis in malignant cells. Arsenic trioxide (ATO) induces apoptosis through multiple mechanisms including generation of reactive oxygen species (ROS), inhibition of anti-apoptotic proteins, and modulation of signaling pathways such as NF-κB. The combination has demonstrated synergistic antiproliferative effects in preclinical studies on hematologic malignancies such as acute myeloid leukemia (AML) and multiple myeloma (MM). Mechanistically, the combination enhances caspase activation, upregulates proapoptotic genes (e.g., CARD9, TRAIL), downregulates antiapoptotic genes (e.g., BCL2), increases mitochondrial membrane permeability, reduces IL-6 secretion, promotes ROS production, inhibits autophagy and abrogates DNA-binding activity of nuclear factor kappa beta (NF-κB). This dual approach may overcome drug resistance by targeting multiple survival pathways simultaneously[1][2][3][4][5][6].

Other names

bortezomib and arsenic trioxidebortezomib plus arsenic trioxideATO + bortezomib