Scientists at the University of Glasgow’s Cancer Research UK Beatson Institute have developed the technique as a research tool to understand how cancer cells die. The significant discovery, published today in Nature Communications, means Mito-priming can be applied to identify new anti-cancer drugs to screen their effectiveness.
In particular, BH3-mimetics are a very promising new class of cancer drugs developed to specifically kill tumour cells. BH3 mimetics target a family of proteins called BCL-2 proteins, which function to keep cancer cells alive.
While not yet in use in clinical practice, BH3-mimetic anti-cancer drugs are showing great promise in late-stage clinical trials, particularly in the treatment of chronic lymphocytic leukaemia (CLL). Researchers at Glasgow’s Institute of Cancer Sciences are hopeful their pioneering mito-priming method can be applied to screen for new drugs to target BCL-2 proteins and help find new ways to kill cancer cells.
The lead author of the paper, Dr Stephen Tait, said: “We have developed a new way to make any cell type sensitive to BH3-mimetic treatment. We term this method mito-priming.
“Mito-priming can be used to rapidly screen for new BH3-mimetics and other anti-cancer drugs, and should improve ways to kill cancer cells. It can also be used to rapidly define the potency and specificity of BH3-mimetics. Finally, the technique will allow us to understand how drug resistance occurs thereby allowing us to prevent this from happening in the first place.
“There is currently a lot of interest in targeting BCL2 proteins in the fight against cancer and there will be new therapies emerging in the future. We are hopeful our new method of mito-priming can be used as a platform to discover new drugs to target BCL-2 proteins.”
The Scientists developed mito-priming by producing equal amounts of toxic and protective BCL-2 proteins in cells.
Dr Tait explained: “Cells in this state are very sensitive to inhibition of protective BCL-2 function by BH3-mimetics, such that they die within a few minutes of drug addiction.”
The paper, entitled ‘Mito-priming as a method to engineer Bcl-2 Addiction’ is published in Nature Communications.
The research was funded by Cancer Research UK, The Biotechnology and Biological Sciences Research Council (BBSRC), Royal Society and Tenovus Scotland.