In a recent study published in the scientific journal Cell Death & Disease, a novel proteasome inhibitor designated D395 was evaluated as a possible treatment for multiple myeloma, a rare form of cancer. A proteasome inhibitor called carfilzomib has been used to treat this disease and has allowed for a meaningful improvement in the survival rate for patients. D395 was found to have some possible advantages in safety compared to carfilzomib. 

About Multiple Myeloma

Multiple myeloma, which is occasionally referred to as plasma cell myeloma, is a blood cancer that affects plasma cells. These are white blood cells that produce antibodies. The overall cause of multiple myeloma is not well understood, however, some risk factors have been identified. These include obesity, family history, smoldering myeloma, and monoclonal gammopathy of undetermined significance. These last two conditions have the potential to develop into multiple myeloma. Symptoms of this cancer include bone pain, infections, anemia, kidney failure, overly thick blood, confusion, fatigue, headaches, and amyloidosis. Treatment includes chemo, stem cell transplant, and other medications for relapsed disease, which is common. Five-year survival rate is 49 percent in the US. To learn more about multiple myeloma, click here.

Study Results

Despite the fact that proteasome inhibitors like carfilzomib are undoubtedly effective, they still carry some disadvantages. Most of the time, cancer will develop resistance to the treatment, meaning that relapse is common. The treatment also can lead to serious side effects, such as cardiotoxicity and neurotoxicity. Cardiotoxicity is of particular concern with carfilzomib. 

D395 was recently discovered and has a different structure compared to carfilzomib. The effect of the two therapies was evaluated side by side in this study on a number of multiple myeloma (MM) cell lines. Overall, D395 appeared to have a similar level of toxicity towards MM cells and intervened in a number of processes that are critical to the propagation and survival of MM cells, ultimately leading to their death. D395 was also able to inhibit tumor growth in a xenograft mouse model. Meanwhile, it has only mild cardiotoxicity in vivo and in vitro. 

Ultimately, these findings suggest that D395 should undergo further evaluation as a possible treatment for multiple myeloma.