Catalog of Effects of Kinase Inhibitors May Aid Development of Anti-Cancer Drugs
Researchers at Fox Chase Cancer Center have catalogued the actions of 178 drugs that have the potential of blocking the activity of enzymes that promote growth of cancer cells, according to an article in the November issue of Nature Biotechnology.
The enzymes, called kinases, transmit signals and control complex processes in human cells. Kinases also function as drivers of a variety of forms of cancer, including mesothelioma. A number of studies suggest that kinases are involved in the gradual transformation of normal tissue in the lining of the lung into malignant pleural mesothelioma after exposure to asbestos. It’s unclear whether one or more kinases promotes the growth of mesothelioma.
More effective therapies and treatment options are needed for mesothelioma which is an aggressive cancer and has a low cure rate.
The scientists at Fox Chase Cancer Center in Philadelphia cataloged drugs including FDA-approved drugs, drugs undergoing clinical trial and laboratory compounds that are designed to block the cancer-promoting activity of any of more than 300 kinases. The body has more than 500 kinases that perform a variety of functions and many kinases are multi-taskers.
Drugs known as kinase inhibitors have the potential to be highly effective anti-cancer drugs that impede the cellular processes that cause cancer. Some cancer patients already receive kinase inhibitors as part of their therapy. And many additional kinase inhibitor drugs are under development. But the reactions of the drugs are complex.
Most kinase inhibitors act on more than one kinase. The drugs may disrupt both the growth of cancer and normal bodily processes at the same time, causing serious side effects such as heart problems.
With the cross-indexed catalog that the Fox Chase scientists have complied, researchers will be able to predict the complex reactions of the kinases inhibitors more accurately. That will allow for the development of drugs that block kinases that promote cancer while aiming to avoid side effects.
“These results have pushed the field closer to finding truly specific inhibitors of the processes that drive cancer,” Jeffrey R. Peterson, associate professor in the Cancer Biology Program at Fox Chase and senior author of the study said in a press release. “We now have a collection of kinase inhibitors that are more well-characterized and understood…. The next step is to use this information to identify specific, effective therapies that stop cancer in its tracks while avoiding healthy processes.”
Until the last few years, researchers didn’t have the tools to observe which kinase a drug acted upon. A new assay technology developed by Reaction Biology Corporation, a Pennsylvania-based provider of drug screening and profiling services, was used to catalog the kinase inhibitor effects.
Each year, approximately 2,500 to 3,000 people in the U.S. are diagnosed with mesothelioma. Most mesothelioma patients are older workers, retirees and veterans who were exposed to asbestos in the workplace. The use of asbestos is now restricted, but asbestos was widely use in the workplaces and in the military from the 1940s through the late 1970s.
Symptoms of mesothelioma typically take 20 years to 50 years to develop so a worker or veteran exposed to asbestos in the 1960s or 1970s may only recently have been diagnosed.
For more information about mesothelioma, click here.
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