Novel combination overcomes drug-resistant multiple myeloma cells

70652986 — Mon, 26 Mar 2007 06:20:05 -0400

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."

Protein packages activate genes

70652986 — Mon, 26 Mar 2007 06:17:33 -0400

It's all in the packaging. How nature wraps and tags genes determines if and when they become active, according to researchers from Harvard and M.I.T. They did the largest, most detailed study to date of the protein structure that surrounds the human genome. Their findings reveal surprising and previously unknown specifics of how genes get switched on during development of the human body and in diseases such as cancer. "Each type of cell in our bodies contains the same genes. What makes them do different things involves which genes are turned on," notes Bradley Bernstein, a pathologist at Harvard Medical School. The analysis shows a striking and surprising exception in the way some critical genes are activated by the protein packaging. The big surprise involves clusters of so-called "HOX" genes, which apparently work in concert to control how we develop in the womb. Instead of being activated individually like most genes, the HOX genes appear to be turned on in groups by massive numbers of tags. HOX genes also are deeply involved in cancer, making the findings particularly important. Some of the proteins that regulate HOX genes are capable of causing or suppressing tumors. "Many of the proteins that regulate these genes can suppress or enhance tumor growth," Bernstein notes. "Some of the genes can cause cancer directly when altered by mutations." "The work we're doing now is very fundamental," he says. "But what we learn about the interactions between chromatin, its tags, and various proteins that interact with them may one day be useful for understanding, diagnosing, and even developing new treatments for some cancers."

all Stuart Schreiber stories

Novel combination overcomes drug-resistant multiple myeloma cells

Protein packages activate genes