Drug-tolerant persisters, de novo mutations and pre-existing resistance are just some of the ways cancers evade the effects of anti-cancer drugs. Can new targets and new dosing strategies tackle evolutionary forces directly to delay the inevitable? Drug-tolerant persisters, de novo mutations and pre-existing resistance are just some of the ways cancers evade the effects of anti-cancer drugs. Can new targets and new dosing strategies tackle evolutionary forces directly to delay the inevitable?