In a new study from Peter MacCallum Cancer Centre and elsewhere, researchers found have discovered an innovative way to dampen severe inflammation.
This uncovers a potential new therapy for inflammatory and autoimmune conditions such as arthritis, psoriasis, and liver disease, as well as some cancers.
The study is published in Science. The lead author of the study is Dr. Omer Gilan.
The team made the discovery while looking for new ways to improve an existing anti-cancer therapy that interferes with processes controlling gene expression inside cells.
Hyperactive cells in cancer and autoimmune diseases often express abnormally high levels of certain genes that drive the disease.
Therapies that can reverse this abnormal gene expression have shown benefit in both cancer and inflammatory conditions.
However, because these processes are also required in normal cells, many of these therapies have unwanted side effects.
This prompts researchers to modify the drug design which led to the development of compounds that are far more specific than their predecessor.
The team was working on a class of drug that shuts down the action of the BET family of proteins, which are currently being evaluated in clinical trials for a variety of cancers across the world.
These drugs work by blocking two sites within BET proteins, rendering the proteins non-functional and killing the cancer cells.
While this therapeutic approach can be effective, it can also lead to some unwanted side effects.
The researchers wanted to determine if they could minimize off-target effects whilst maintaining anti-cancer activity.
To do this, they worked with the team of scientists at GSK who designed compounds to interfere with just one of the sites at a time.
To their surprise, they discovered that when they selectively blocked the second BD2 site the drug no longer had anti-cancer activity but became a potent suppressor of immune cell function.
The treatment was well tolerated by the mice and their inflammatory disease was vastly improved, and in some cases was even more effective than currently available treatments.
If confirmed in humans, the findings could have a major impact on people suffering from both malignant and inflammatory diseases in Australia and around the world.
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