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Mesothelioma News | 2007
Overexpressed Protein is Prevalent in Mesothelioma Cells: Recent study uncovers links to targeted therapies
A recent published study* shows, for the first time, a connection between malignant mesothelioma and the overexpression of a particular genetic protein.
In an attempt to gain a better understanding of this particularly deadly type of cancer on a cellular level, a team from the University of California, San Francisco Comprehensive Cancer Center sought to identify genetic material in mesothelioma cells that occurs at higher levels than the same material does in non-cancerous cells (that is overexpressed).
What scientists discovered could be an important step in developing treatments that target mesothelioma cells in very early stages.
A strong and consistent clue
Jae Kim, MD, primary investigator says "In the biological sense, we don't know why mesothelioma develops or why it's so aggressive."
"The molecular pathways disrupted in this disease are vastly different from the ones disrupted in many other cancers so we need to find mesothelioma's specific biologic mechanisms in order to come up with new targeted therapies."
In conducting gene-expression analyses the team was able to identify patterns of genetic expression that are unique to mesothelioma cells, in addition to the specific genes involved in the disease, Kim says.
Researchers looked at nine mesothelioma cell lines (tumor cells that are cultured and manipulated so that they continue to divide) and eight tumor samples ("fresh" cells derived from mesothelioma tumors).
They identified a gene that was consistently and strongly expressed in the cell lines and the tumor samples: stathmin, a cellular protein previously implicated in other aggressive forms of cancer.
The gene, stathmin, was overexpressed in seven of the nine cell lines, and seven of the eight tumor samples.
Kim explained, "We were surprised that this occurrence was so prevalent throughout our study - and that the stathmin gene was so strongly and consistently overexpressed in both types of mesothelioma cells," as the protein is an important player in the life cycle of a cell.
"Stathmin's fundamental role is to regulate a cell's cytoskeleton, which controls the cell's architecture and instructs the cell to grow, develop, reproduce, and divide," says Kim. "Because cancer cells grow and divide much faster than normal cells, the cytoskeleton link is critical - and many existing cancer drugs specifically target the cytoskeleton."
Interestingly, there are other studies that suggest that stathmin overexpression may cause cancer cells to become less sensitive to some forms of chemotherapy, Kim says, "which might explain why mesothelioma often doesn't respond to these agents."
"We Are Making Progress"
The findings of the group could be important to the study and treatment of other types of cancer, as well, says Kim.
"The data that we've acquired provide further evidence that stathmin is important in a variety of cancers - especially the more aggressive ones - and it is definitely a target worth investigating further."
Jae Kim's advice to mesothelioma patients and people at risk for the disease is to stay optimistic.
"The scientific community is learning more about mesothelioma every day," he says. "We're discovering new molecular targets, and there are drugs being developed to target different proteins and genes. We are making progress, and individuals with this disease should continue to have hope."
