Getting to the finish line with mTORC1-targeted therapy.

The mammalian target of rapamycin (mTOR) pathway is activated in the majority of human malignancies and thus seems a likely therapeutic target. However, this pathway is genetically complex, complicating studies using pharmacologic mTOR inhibitors. In this issue of the JCI, Hoshii et al. examined mice deficient in one of the mTOR effector complex proteins, Raptor, to elucidate the role of mTORC1 in leukemia. They convincingly demonstrate that Raptor deficiency, with consequent mTORC1 inhibition, blocks differentiation of leukemia cells and prolongs survival, but also allows a population of leukemia-initiating cells to persist in what appears to be a state of dormancy. Translating this new understanding into effective therapeutic strategies will require further study of the molecular mechanisms that underlie these processes.