Novel combination overcomes drug-resistant multiple myeloma cells

The researchers hope to move rapidly to clinical trials of the therapy, a combination of the drug Velcade and an experimental compound that was designed by researchers at the Broad Institute of the Massachusetts Institute of Technology and Harvard University.

The report demonstrates that the combination was more than twice as effective as either drug alone in killing resistant cells from patients’ bone marrow.

“This is not just another drug – this is a whole new approach to treating multiple myeloma,” said Kenneth Anderson, M.D., senior author of the paper.

Velcade is the first in a class of so-called proteasome inhibitors, which destroy cancer cells by blocking the proteasome, a disposal mechanism that rids the cell of abnormal proteins. Cells in which the proteasome is jammed eventually commit suicide, triggered by the accumulation of proteins, explains Anderson.

However, many cancer cells are resistant to proteasome inhibitors like Velcade. Recent studies have revealed an alternative protein-disposal complex, the aggresome, that may take over enough of the job when the proteasome falters to allow the cells to survive.

Therefore, the Dana-Farber researchers suggested that blocking both protein disposals at once might get around this resistance mechanism. Scientists led by one of the study’s authors at the Broad Institute designed a drug that blocks an enzyme critical to the aggresome’s ability to function.

These highly promising results, wrote the researchers, “provide the framework for clinical trials designed to enhance sensitivity and overcome resistance to bortezomib [Velcade], thereby improving patient outcome in multiple myeloma.”