Altered cancer drug takes the fight to inflammatory diseases
Inflammation is a major focus of much medical research, with its links to arthritis, liver disease, cancers and many more illnesses. A new study carried out at Australia’s Peter Mac Cancer Centre has provided a possible new pathway forward, revealing that drugs under development to treat cancer could be used to temper inflammation in a powerful way.
The Peter Mac Cancer Centre researchers were working with scientists at GlaxoSmithKline to improve on a class of anti-cancer drugs that target hyperactive cells in cancer and autoimmune diseases, in which the immune system mistakenly attacks the body and drives inflammation.
The team was looking at a class of drugs that shut down a family of proteins identified as targets in cancer called Bromodomain and Extra-Terminal, or BET, proteins. Drugs that inhibit these proteins are being tested against a variety of cancers in a number of trials around the world and work by blocking two sites within the BET proteins to render them useless, in turn killing the cancer cells.
One of the drawbacks of the approach, however, is that healthy cells also depend on BET proteins, resulting in some unwanted side effects. To limit these, the research team was tweaking the design of the drugs in a way they hoped would preserve the anti-cancer benefits of the compounds but leave healthy cells unharmed.
This led them to engineer modified versions that blocked just one of the BET sites at a time, a process of trial and error that led to an unexpected discovery. The team found that that a drug designed to selectively block the second BET site lost all anti-cancer potential but gained new skills as a powerful suppressor of immune cell function, as observed in rodents.
“When the selective BD2 blocker was given to mice with inflammatory conditions that mimic human auto-immune diseases including arthritis, psoriasis and liver disease, it acted to suppress immune function in a potent and specific way,” says study lead author Dr Omer Gilan.
So specific was the treatment that it was well tolerated by the mice, with their inflammatory diseases greatly improving as a result. Perhaps even more so than the results themselves, the team is particularly excited about this newfound knowledge of how BET proteins function, and how it could result in entirely new options for a range of treatments, though they note testing in humans is still a ways off.
“Another really great outcome of this study is that we have also finally shed light on the biological mystery of why these BET proteins have two almost-identical regions that are conserved throughout evolution,” explains senior author on the study, Mark Dawson. “Importantly, by showing that each region has a completely distinct and non-redundant role, we have discovered an entirely new approach to tackling diseases such as cancer and inflammation.”
The research was published in the journal Science.
Source: Peter Mac Cancer Centre