Anti-tumor activity in multiple myeloma after Velcade (bortezomib) treatment has been thought to result from the drug inhibiting a protein complex that regulates the immune response. Now, scientists think that Velcade works through other mechanisms.

The complex is known as NF-kappaB. When it is activated, it causes the body’s cells to respond to foreign particles and cause an immune response. Initially, Velcade has been thought to work by blocking the function of enzymes, including the complex NF-kappaB, that break down proteins in the cell. Because inhibition of these enzymes causes cellular proteins to aggregate or clump together, the cell cannot survive and tumor growth is suppressed.

According to a study published in the journal Blood in July 2009, Velcade may interact with other proteins that actually cause NF-kappaB to be expressed, not suppressed. In other words, Velcade’s effects on multiple myeloma cells might not be caused by NF-kappaB inhibition.

The study hypothesizes that multiple myeloma cell death might be caused from a buildup of proteins. Myeloma cells may become sensitive to stress from this buildup. With further studies, scientists may be able to determine the exact mechanism by which Velcade works. Understanding this can lead to more effective therapies.

For more information about these findings, see the commentary and research article (abstract) in the journal Blood.