proteasome inhibitor
Meaning of proteasome inhibitor: Cells that manufacture antibody by the ton depend most on clearing protein waste, which is why myeloma is unusually sensitive to the block.
Definition of proteasome inhibitor
A proteasome inhibitor is a drug that blocks the proteasome, the barrel-shaped machine every cell uses to shred proteins that are damaged, faulty or no longer wanted. With disposal jammed, unwanted proteins pile up, stress signals build and the cell dies. The class is a standard part of treatment for multiple myeloma and is also used in mantle cell lymphoma.
What does the proteasome normally do?
Every protein in a cell has a limited life. Ones that are misfolded, damaged or finished with are labeled with a small tag called ubiquitin, and the labeled protein is fed into the proteasome, a hollow barrel lined with cutting enzymes that reduces it to short fragments. The process is not simply housekeeping. Many controls on cell division, on inflammation and on cell death work by destroying a regulator at a precise moment, so blocking disposal disrupts those controls as much as it disrupts the cleanup.
Why are myeloma cells so vulnerable?
A myeloma cell is a plasma cell, and plasma cells exist to pour out antibody. Production on that scale generates a constant stream of misfolded protein that has to be destroyed as fast as it appears. The disposal system in these cells is therefore already close to its limit, and a modest block tips them into a stress response ending in cell death, while ordinary cells carrying lighter loads survive the same exposure. That margin is what makes the class useful rather than uniformly toxic.
How do the drugs in the class differ?
| Drug | Route | Binding | Prominent effect |
|---|---|---|---|
| Bortezomib | Injection | Reversible | Nerve damage in the hands and feet |
| Carfilzomib | Injection | Irreversible | Heart and blood pressure effects |
| Ixazomib | By mouth | Reversible | Digestive upset, low platelets |
Is it the same as a protease inhibitor?
No, and the names sit close enough to be mistaken for one another constantly. A protease inhibitor blocks an individual protein-cutting enzyme, such as the one a virus needs in order to assemble itself. A proteasome inhibitor blocks the entire disposal complex, which contains protein-cutting activity but is a large assembly rather than a single enzyme. The targets, the diseases treated and the side effects have nothing in common.
Used in a sentence
A proteasome inhibitor was combined with a steroid and an immunomodulatory drug.
Good to know
The class is established treatment rather than investigational, and its members differ in their characteristic harms, with peripheral nerve damage prominent for bortezomib and cardiovascular effects for carfilzomib.
Word origin
Where “proteasome inhibitor” comes from
Proteasome was coined from protease, an enzyme that cuts proteins, and the Greek soma, meaning body, for the particle carrying out the cutting.