A class of medications known as proteasome inhibitors are used to treat cancer, particularly in treating certain blood malignancies, including multiple myeloma and mantle cell lymphoma. Proteasomes, a cellular component in charge of protein breakdown, are targeted, and proteasome inhibitors inhibit their activity as part of their mechanism of action.
The main job of the proteasome, a large protein complex located in the cytoplasm and nucleus of cells, is to break down unneeded or damaged proteins. This procedure is crucial for preserving cellular homeostasis, controlling protein levels, and getting rid of aberrant or misfolded proteins that might harm the cell.
As a result of the proteasome's action being blocked by proteasome inhibitors, proteins that ought to be destroyed accumulate. As a result, several crucial cellular functions are interfered with, ultimately resulting in cancer cells dying. The following are the crucial phases in proteasome inhibitors' mode of action:
- Protein degradation is prevented by proteasome inhibitors, which bind to the catalytic subunits of the proteasome, which break down the targeted proteins. By doing this, they stop the proteasome from destroying numerous proteins involved in DNA repair, cell survival, cell cycle regulation, and other crucial cellular processes.
- Damaged proteins accumulate in the cell when the proteasome is stopped, which is why they should have been destroyed. This buildup causes cellular stress, which activates a physiological response known as the unfolded protein response (UPR).
- Apoptosis (planned cell death) and cell cycle disruption: The buildup of damaged and improperly folded proteins activates UPR pathways, obstructing cell cycle advancement. UPR acts as a defense mechanism in healthy cells to deal with cellular stress, but it can lead to their demise in cancer cells.
- Selective toxicity to cancer cells: Proteasome inhibitors have shown a remarkable ability to target cancer cells while sparing healthy cells selectively. Cancer cells are particularly sensitive to proteasome inhibition due to their higher dependence on the proteasome for the degradation of proteins associated with cell proliferation and survival.
The most well-known proteasome inhibitor used in cancer treatment is bortezomib. Bortrac 2mg Injection is a chemotherapy medication that belongs to the class of medicines called proteasome inhibitors. Since its development, other proteasome inhibitors have been developed and approved for clinical use, such as carfilzomib and ixazomib. These drugs have significantly improved the outcomes for patients with certain types of blood cancers and continue to be an important component of modern cancer therapies.
