Explaining and exploiting the spectrum of isocitrate dehydrogenase driver mutations in different tumour types

Cancers mostly develop when cells in the body acquire mutations to their DNA. Mutations in genes called isocitrate dehydrogenase (IDH) cause many cancers, of which some, including brain tumours and leukaemia, have very poor survival. Different types of cancer have different types of IDH mutation and we want to find out why. IDH mutations produce a cancer-causing substance called D2HG, but different IDH mutations are more efficient at this process than others, and the most commonly found mutations do not necessarily make the most D2HG.

We shall relate D2HG levels to specific IDH mutations, finding out which mutations and D2HG levels most favour tumour growth in different parts of the body. We shall also test whether too much D2HG stops tumours from growing.

This work may lead to new anti-cancer therapies based on increasing D2HG to a level that is toxic to cancer cells.