ESR1 and breast carcinoma: It has been suggested that the increased activation of mTOR, possibly through the PI3K/AKT pathways, plays a role in the endocrine resistance exhibited by some ERα+ breast cancer cells, and that the inhibition of mTOR signaling with rapamycin could restore sensitivity to 4-OHTAM, an inhibitor of the estrogen pathway, in laboratory models of resistance [45].