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May 12, 2020 /
PRNewswire
BIOON // Researchers from the Peter McCallum Cancer Center have found an innovative way to suppress severe inflammation in mice, offering a potential new way to treat inflammation and autoimmune diseases such as arthritis, psoriasis, liver disease, and some cancers the study was carried out by Professor Mark Dawon's lab in collaboration with scientists from glaxoSmithKline
(GSK), , who discovered the problem while looking for new ways to improve an existing anti-cancer therapy Existing anti-cancer therapies interfere with the process of controlling gene expression within cells in cancer and autoimmune diseases, certain genes of overactive cells often express abnormally high levels of genes, which are the cause of the disease Treatments that can reverse this abnormal gene expression have benefits in both cancer and inflammation image source: http://cn.bing.com
However, because these processes are also necessary in normal cells, many of these treatments have side effects, prompting researchers to modify drug designs to develop compounds that are more specific than previous treatments Dr Omer Gilan, lead author of the study, said: "The results are actually a surprise To advance the research, the drug chemistry team GlaxoSmithKline's initially designed the new compound series to try to improve existing cancer treatments We didn't really focus on inflammation at first "
team was working on a drug that inhibits the activity of BET family proteins -- drugs that are currently being in clinical trials of various cancers around the world these drugs work by blocking two sites in the BET protein, causing the protein to lose function and kill cancer cells although this treatment may be effective, it can also cause unnecessary side effects researchers want to determine whether they can minimize off-targeteffects while maintaining anti-cancer activity To do this, they worked with a team of scientists at GlaxoSmithKline, which designed compounds that could interfere with only one site at a time surprised them, they found that when they selectively blocked the second BD2 site, the drug was no longer cancer-resistant, but became an effective immunocellular functional inhibitor "When selective BD2 receptor blockers were given to mice with inflammatory conditions similar to those of human autoimmune diseases, including arthritis, psoriasis and liver disease, it effectively inhibited immune function," said Dr gilan, "
mice are well tolerated for this therapy, and their inflammatory diseases have improved significantly, in some cases even more effectivethan the therapies currently available " another significant achievement of this study is that we have finally solved the biological mystery of why these BET proteins have two almost identical regions throughout evolution Importantly, by revealing that each region has a completely different and non-redundant effect, we have found a new way to deal with diseases such as cancer and inflammation Professor Mark Dawon, author of the study' newsletter, explained if confirmed in humans, the findings will have a significant impact on patients with malignant and inflammatory diseases in Australia and around the world Professor Dawon, , said: "There is still some way to go before this new treatment can be tested in humans, but the evidence for principled research in mice is certainly promising "
this paper, entitled "Selective targeting of BD1 and BD2 of the BET protein in cancer and immune-for-physiat", was published in the journal Science (biovalleybioon.com) References: New to ting arthriti and other rheae
Omer Gilan et al.
Selective targeting of BD1 and BD2 of the BET protein in cancer and immuno-fi, Science (2020) DOI: 10.1126/cience.aaz8455