Proteasome Inhibitors (PIs)

Proteasome inhibitors (PIs) are a type of drugs that block the function of the proteasome. The proteasome acts as a “garbage disposal” in cells and breaks down excess or damaged proteins. This degradation process produces short peptides that can be recycled to form new proteins.

When a healthy cell produces an excess amount of protein, the proteasome breaks down and eliminates these unnecessary proteins. If this process is disturbed, proteins build up in the cell, inducing cell death. Multiple myeloma cells produce excessive amounts of proteins called M proteins. As these proteins are useless, they need to be processed by the proteasome. As a result, multiple myeloma cells (and cancer cells in general) exhibit a higher level of proteasome activity. By inhibiting the activity of the proteasome, M-proteins build up in the cell, inducing cell death in myeloma cells.

For the moment, three different PIs are used in the treatment of patients with multiple myeloma: bortezomib, carfilzomib and ixazomib. As with all other anticancer agents, PIs come with a number of side effects. These include gastrointestinal problems (e.g., nausea, vomiting, diarrhea, constipation), back pain and swelling of hands and feet. In addition to this, PIs can reduce the level of platelets in the blood, which causes patients to bruise or bleed easily. In a proportion of patients, PIs may also cause damage to certain nerves, leading to numbness or a tingling feeling in fingers and toes (peripheral neuropathy).