Given the promise of combination cancer therapy, many drug discovery programmes are aiming to identify compounds with additive or synergistic effects. Using Drosophila, Edwards et al. report a system to screen for agents that enhance the anti-cancer effects of radiation. Following initial screens revealing microtubule poisons as candidates, they analyse one candidate, maytansinol, in Drosophila cells and larvae, and in human cancer cells. Their results show that this agent’s actions are p53-dependent and that they differ in vitro versus in vivo, highlighting the importance of studying drug effects in a whole organism.