Using in vitro and in vivo models, we demonstrated that mTORC1 is the major kinase signaling downstream of RON in both ER+ and TNBC models, and that combined blockade of RON and mTORC1 may offer benefit to breast cancer patients whose tumors overexpress RON and are either at high risk of recurrence or have already progressed to the metastatic stage. The gene discussed is ESR1; the disease is breast carcinoma.