Figure 4. Autocrine/paracrine RANKL/RANK signaling: A shared denosumab-responsive CSC trait across multiple breast cancer subtypes.

Tumor-initiating cell from genetically diverse pre-cancerous and breast cancer subtypes might share, to a greater (BRCA1 haploinsufficiency) or lesser extent (EMT) and HER2), a common addiction to hyperactive RANKL/RANK signaling, which allows their survival and self-renewal in a CSC state. This observation might inaugurate a new era of cancer prevention and treatment capable of producing sustained effects based on RANKL-targeting approaches.