A study led by Dr Christian Frezza (MRC Cancer Unit) has revealed the function of fumarate, a metabolite accumulated in fumarate hydratase-deficient renal cancers. The research published in Nature, showed that fumarate activates a signalling cascade, initiated by the hypermethylation of a small non-coding RNA called microRNA 200, which leads to a change in cell type, a process involved in tumour initiation and metastasis.

Fumarate has  recently been defined an “oncometabolite” because of its role in tumorigenesis. This work, with Dr Marco Sciacovelli as first author, revealed an unexpected link between metabolism and epigenetics. From a clinical perspective, it provides a potential explanation for the high malignancy of tumours where fumarate hydratase is lost. Understanding how to pharmacologically block fumarate-driven cellular changes would be a priority in potentially preventing cancer metastasis in this aggressive form of renal cancer. This work was possible thanks to the teamwork of many scientists from the Clinical School, Cambridge Cancer Centre and the European Bioinformatics Institute.