Possible Therapeutic Potential of Disulfiram for Multiple Myeloma

Drozdkova, Denisa Weiser; Trtková, Kateřina Smešný

doi:10.3390/curroncol28030193

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…It has also been suggested that upregulation of IRE1α-XBP1 pathway is related to immune modulation via NF-κB signaling [28], which supports the immunostimulatory effects of PIs. Recently, the complex of disulfiram and copper (DS/Cu) is also reported to induce apoptosis of myeloma cells by inhibiting proteasome [29,30]. In particular, copper (II) ions suppress peptidase activities of 20 S proteasomes [31].…”

Section: Reagentsmentioning

confidence: 99%

Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells

Matsushita,

Kashiwazaki,

Kamiko

et al. 2023

Pharmaceuticals

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Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activation of acquired immunity against cancer cells. ICD was originally reported in solid tumors, and there have been few reports on ICD in multiple myeloma (MM). Here, we showed that proteasome inhibitors, including carfilzomib, induce ICD in myeloma cells via an unfolded protein response pathway distinct from that in solid tumors. Additionally, we demonstrated the potential impact of ICD on the survival of patients with myeloma. ICD induced by proteasome inhibitors is expected to improve the prognosis of MM patients not only by its cytotoxic effects, but also by building strong immune memory response against MM cells in combination with other therapies, such as chimeric antigen receptor—T cell therapy.

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