Researchers, reporting in the journal Cancer Research, have discovered that adding the drug salubrinal could dramatically improve Velcade’s effectiveness in treating multiple myeloma. Although this study did not involve human subjects, the findings provide a promising foundation for further research.

Velcade ^[1] (bortezomib), a proteasome inhibitor, is an FDA-approved novel therapeutic agent for treating multiple myeloma. In clinical trials, Velcade in combination with other agents has achieved high treatment response rates as both frontline and relapse therapy.

Despite Velcade’s demonstrated success at achieving response or even remission, even patients who respond well often relapse after Velcade therapy. Researchers now understand that Velcade’s mechanism of action, while enabling myeloma cell destruction, also simultaneously induces as many as 50 percent of myeloma cells to enter a dormant state. These dormant cells avoid destruction, and they can reawaken months or years after treatment to cause cancer recurrence.

Adding the drug salubrinal to a therapeutic regimen, either concurrently or consecutively to Velcade, could greatly enhance Velcade’s effectiveness. In the current study, researchers exposed laboratory myeloma cells to either Velcade alone or to a Velcade/salubrinal combination. The combination treatment killed 90 percent of the myeloma cells upfront, compared to only 50 percent for Velcade alone.

Specifically, salubrinal functions by blocking the cellular signals necessary for Velcade-induced dormancy. When administered simultaneously with Velcade, it increases initial cancer cell destruction, and a second administration after Velcade therapy “roots out” and destroys residual dormant cells.

Currently, no human studies with salubrinal have occurred. The drug is not yet approved by the FDA as a treatment for any medical condition, and no clinical trials are presently underway. However, other studies have evaluated salubrinal in mice models, including as therapy against the herpes virus and for neurological disorders.

Significantly, although the present myeloma study only involved laboratory cells, salubrinal proved effective at dosage levels that would not be toxic to humans. These results lay the groundwork for further research into salubrinal’s clinical potential as a myeloma therapy.

For more information, see the February issue of Cancer Research ^[2] (article abstract viewable for free; full article available for a fee).