At the same time, denosumab can interfere with the crosstalk between RANKL-producing “sensor” cells and RANK+ “tumor-initiating responder cells.” Interestingly, metformin synergistically increased the sensitivity of this type of breast cancer to denosumab (Cuyàs et al., 2017). The gene discussed is TNFRSF11A; the disease is breast carcinoma.