Novel Anti-Cancer Agents for Multiple Myeloma

For many years, dexamethasone has been at the forefront of multiple myeloma therapy. Belonging to a class of drugs called corticosteroids, it exhibits anti-inflammatory, immunosuppressive, and anti-tumor effects. As a long-standing standard of care in the management of myeloma, many newer agents are typically used in combination with dexamethasone.

Three of the most important novel agents for the treatment of multiple myeloma patients are bortezomib, thalidomide and lenalidomide.

Bortezomib inhibits enzymatic complexes, known as proteasomes, which mediate the degradation of many proteins in the cell.

Myeloma cells depend upon proteasomal degradation of a specific subset of proteins in order to regulate and promote their own survival. One such protein is IκB, which serves to inhibit the transcription factor, NF-κB.

When the degradation of IκB is blocked by bortezomib, it accumulates in the cell and actively inhibits the NF-κB pathway, an important process for myeloma cell survival.

By comparison, while the mechanisms of action of thalidomide and lenalidomide are not yet fully understood, they appear to work through multiple means.

First, these agents are immunomodulatory through their global effects on cytokine activity and enhancement of anti-tumor immunity.

Second, they are anti-angiogenic through the blockage of VEGF and bFGF signaling pathways.

Third, they are pro-apoptotic by inhibiting the growth and survival of both stromal and myeloma cells.

Bortezomib, thalidomide, and lenalidomide as novel anti-multiple myeloma agents has changed the management of disease.