Scientists from the Protein Dynamics group at ISAS recently helped to identify two potential drugs for lung cancer. They are so-called RET inhibitors: The protein kinase RET is an interesting target for anti-cancer drugs, because the RET gene is often mutated in tumour cells, producing an altered RET kinase that is often fused to other proteins. As RET is not affected in healthy cells, the altered forms in tumour cells can be selectively attacked by drugs. However, current anti-RET drugs only show a very limited activity.
In their paper now published in "Science Translational Medicine", a team of scientists from the University Clinic Cologne, ISAS, and other international partners analysed different RET fusions and also discovered two potent RET inhibitors. They did a detailed investigation of their mechanism of action, and by using efficient computer models and phosphoproteome analyses, they elucidated two potential pathways that might explain the limited activity of other RET inhibitors.
The paper is available online under: http://stm.sciencemag.org/content/9/394/eaah6144