Mesothelioma treatment today is basically made up three options: surgery, chemotherapy, or radiation. More targeted therapies that address the biological factors triggering mesothelioma growth might be a much more precise and effective way to combat this difficult-to-treat cancer, according to a recent article in Connective Tissue Research.
Mesothelioma is so challenging to treat because it is often diagnosed at a late stage, and because it can take many biological forms. Current mesothelioma treatments were originally designed for other types of cancers, without considering factors that may be specific to mesothelioma. That may be why many patients only partially respond to treatment, and the average survival is just 12 months after diagnosis.
The key to prolonging the lives of mesothelioma patients may lie in more specific “targeted therapies” that address the mechanisms that drive disease progression. “The term ‘targeted therapy’ refers to a new generation of anti-cancer drugs designed to interfere with a specific molecular ‘target,’ most often a protein or a receptor that is believed to have a critical role in tumor growth,” says lead study author Katalin Dobra, MD, PhD, a researcher in the Department of Laboratory Medicine at the Karolinska Institutet in Stockholm, Sweden.
“Targeted cancer therapy takes advantage of our recent knowledge of the key mechanism that the malignant [cancerous] cell needs for its survival, and uses the special properties of mesothelioma cells to design novel therapeutic strategies,” Dr. Dobra says.
The process starts with molecular screening to identify the characteristics of a tumor and how it behaves—what causes it to grow and spread. Then researchers test various therapies on cells in the laboratory to see if they can interfere with that process. Not until then can a new cure be tested on patients in clinical trials.
So far, Dr. Dobra’s team has identified three possible molecular targets, each with its own potential treatment:
• Proteasome-subunits are groups of enzymes that regulate cell progression and death. Potential treatment: Drugs called proteasome inhibitors have been shown to halt the growth of mesothelioma cells.
• The thioredoxin system contains components that are produced differently in cancerous and noncancerous mesothelial cells, and it is thought to contribute to the survival of mesothelioma cells. Potential treatment: In collaboration with other groups, Dr. Dobra has shown that the mineral selenite may trigger mesothelioma cell death while sparing healthy cells.
• Proteoglycans (PGs) are a class of proteins that differ based on the type of mesothelioma cell. They work by affecting the growth factors that help mesothelioma cells grow and divide. Potential treatment: Oligosaccharide sequences, which are made up of chains of sugar molecules, might interfere with the work of PGs. One of these targeted approaches, proteasome inhibitors, is now being tested in clinical trials. The other two methods are also promising, but more research is needed before they can be tested on patients. Additional tumor targets are also being investigated.
The next step in the research is to combine various treatments—both traditional and experimental—to see which ones are most effective at targeting mesothelioma tumors, Dr. Dobra says. Attacking the tumors from as many different approaches as possible may offer the greatest benefit to mesothelioma patients.
Source: Dobra K, Hjerpe A. Targeted therapy—possible new therapeutic option for malignant mesothelioma? Connect Tissue Res. 2008;49:270-272.