There is a lot of interest in using multicellular tumor spheres (MCSs) in screens, as opposed to cells cultured on 2D substrates, to find new lethal small molecules that may be more likely to be active against tumors in vivo. This interesting paper identifies a new compound, VLX600, that is selectively lethal to the central 'core' area of MCSs formed from HCT116 cells. It appears to disrupts mitochondrial metabolism, but the target remains unclear.