The interplay between cell signalling and the mevalonate pathway in cancer

Key Points Mevalonate (MVA) pathway metabolites are essential for cancer cell survival and growth. Expression of the genes encoding MVA pathway enzymes is controlled by the sterol regulatory element-binding protein (SREBP) family of transcription factors. In cancer cells, oncogenic signalling pathways deregulate the activity of the SREBP transcription factors and MVA pathway enzymes. Deregulated production of MVA pathway metabolites modulates multiple signalling pathways in cancer cells and contributes to transformation. Clinical trials to evaluate the utility of MVA pathway inhibitors as anticancer agents have shown responses in some, but not all, patients; discovering biomarkers to identify responders and developing combination therapies will further enhance the utility of these inhibitors. Inhibiting the SREBP transcription factors is a promising strategy to increase the efficacy of MVA pathway inhibitors as anticancer therapeutics, and also potentially to combat resistance to MVA pathway therapies.