A study led by Ludwig Scientific Director Chi Van Dang and his colleagues at Stanford University uncovered a novel vulnerability in tumors that are driven by a common cancer gene known as MYC. Such cancers, the researchers reported in a September paper in Cell Metabolism, are highly dependent on the cell’s machinery for making fats and other lipids, and this dependency might be exploited for therapy. MYC, they found, controls the gene expression required for almost every stage of lipid synthesis, from the generation of precursor molecules to the construction of complex lipids. It does so by boosting the expression and then ramping up the activity of SREBP1—a regulator of gene expression that controls lipid production. The researchers also identified a lipid signature associated with MYC-driven cancers and, using mouse models of MYC-induced tumors, showed that cancers of the blood, lungs, kidneys and liver are highly dependent on fatty acid synthesis. Inhibiting an early step of that process led to tumor regression. MYC is the third most amplified gene in human cancers and Chi and his colleagues at Stanford University show that even tumors driven by other oncogenes are susceptible to the inhibition of fatty acid production if they indirectly activate MYC.
This article appeared in the November 2019 issue of Ludwig Link. Click here to download a PDF (1 MB).