01 October 2018

Scientists have discovered the potential of using lung cancer drugs as new therapies for acute leukaemias.

Professor Pat Eyers and colleagues at the University of Liverpool made the discovery whilst looking for drugs which target a protein called TRIB2 - a ‘pseudokinase’ protein which is unable to catalyse chemical reactions. Pseudokinases play many roles in cell signalling, development and cancer, including the ability to promote cell survival.

TRIB2 is linked to promoting survival and drug resistance in solid tumours and blood cancers, in particular acute myeloid and acute lymphoblastic leukaemias, where there is an urgent need for targeted therapeutics for patients who develop resistance to standard treatments.

Working in collaboration with scientists at the Universities of Georgia and North Carolina, Chapel Hill, USA, the team screened a panel of 367 protein kinase inhibitors. Of a number of compounds which were found to make TRIB2 unstable, two drugs, afatinib and neratinib, are approved treatments for lung cancer. The researchers then showed that treating an acute myeloid leukaemia cell line with afatinib or neratinib lead to cell death.

The drugs in question were originally designed to block Epidermal Growth Factor Receptor (EGFR) and related proteins, such as HER2.

The results of this work, published in Science Signaling, provide the research community with new tools to further investigate the role of TRIB2, and could be used to design new treatments for solid tumours and blood cancers which depend on TRIB2 for survival.

Professor Eyers said: "A long-standing goal in cancer research is drug-induced degradation of oncogenic proteins.

"Our study highlights how information obtained with 'off-target' effects of known drugs is potentially useful because it might be exploited in the future to help eliminate a protein that is involved in a completely different type of cancer." 

Source: Foulkes, D.M., Byrne, D.P., Yeung, W., Shrestha, S., Bailey, F.P., Ferries, S., Eyers, C.E., Keeshan, K., Wells, C., Drewry, D.H., Zuercher, W.J., Kannan, N., Eyers, P.A. (2018) “Covalent inhibitors of EGFR family protein kinases induce degradation of human Tribbles 2 (TRIB2) pseudokinase in cancer cells”, Science Signaling, available at doi: 10.1126/scisignal.aat7951


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